Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive t...Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.展开更多
Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and ...Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.展开更多
Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been repor...Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.展开更多
Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of bindi...Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of binding and fusionwith the oocyte. During capacitation various biochemical and biophysical changes occur in the spermatozoa and thespermatozoal membranes. Ions and ion channels also play important roles in governing the process of capacitation bychanging the fluxes of different ions which in turn controls various characteristics of capacitated spermatozoa. Alongwith the mobilization of ions the generation of free radicals and efflux of cholesterol also plays an important role in thecapacitation state of the spermatozoa. The generation of free radical and efflux of cholesterol change the mechano-dynamic properties of the membrane by oxidation of the polyunsaturated lipids and by generating the cholesterol freepatches. The process of capacitation renders the spermatozoa responsive to the inducers of the acrosome reaction. Theglycoprotein zona pellucida 3 (ZP3) of the egg coat zona pellucida is the potent physiological stimulator of the acro-some reaction; progesterone, a major compoent of the follicular fluid, is also an induce of the acrosome reaction.The inducers of the acrosome reaction cause the activation of the various ion-channels leading to high influxes of calci-um, sodium and bicarbonate. The efflux of cholesterol during the process of capacitation alters the permeablity of themembrane to the ions and generate areas which are prone to fusion and vesculation process during the acrosome reac-tion. Ths review focuses mainly on effects of the ion and ion-channels, free radicals, and membrane fluidity changesduring the process of capacitation and acrosome reaction. (Asian J Androl 1999 Sep; 1: 95-107)展开更多
Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain a...Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2＋-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups： adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/I expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2＋ influx, inhibit calcium overload, and diminish Ca2＋ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.展开更多
Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a cha...Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be ＂lethal＂, which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings： M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.展开更多
The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly...The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly fully dehydrated ions, whereas only two of such binding sites exist in the non-selective NaK channel, and none of them is found in the NavAb sodium channel. Here we show that the stability of the selectivity filters in these tetrameric cation channels is inversely correlated with the number of stable binding sites by extensive molecular dynamics simulations. While the presence of coordinated ions is crucial for the selectivity filters of the KcsA and NaK channels to stabilize the conformations in their crystal structures, the selectivity filter of the NavAb channel shows higher stability, independent of the presence of ions. We further show that the distinct repulsive electrostatic interactions between negatively charged oxygen atoms in the selectivity filter which form the stable binding sites are responsible for the different stability of these cation channels. The hydrogen bonding networks between residues in the selectivity filter and its adjacent pore helix also play an important role in maintaining stability. Together, these results provide important mechanistic insights into the structural stability of the selectivity filters in typical cation channels.展开更多
OBJECTIVE:To explore how Qingfei Zhisou oral liquid(清肺止嗽口服液,QFZS)adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences.METHODS:Dry yeast was subcutaneously...OBJECTIVE:To explore how Qingfei Zhisou oral liquid(清肺止嗽口服液,QFZS)adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences.METHODS:Dry yeast was subcutaneously injected at 10 mL/kg to establish the pyrexia model.We randomly divided 60 Sprague-Dawley rats into five groups:control,model,positive,low dose of QFZS and high dose of QFZS.Inflammatory proteins were evaluated by Western blotting and immunohistochemistry.For the examination of the endogenous metabolites,enzyme linked immunosorbent assay and ultra-high-performance liquid chromatography high-resolution mass spectrometry were employed.RESULTS:QFZS significantly reduced rats'body temperature within 6 h after dry yeast injection and reduced the secretion of the arginine vasopressin,cyclic adenosine monophosphate,prostaglandin E-2,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1βin serum.Meanwhile,we identified 41 metabolites between the model and QFZS groups,including arachidonic acid and lysophospholipids.QFZS restored normal arachidonic acid levels.Based on the differential metabolite enrichment analysis,QFZS's antiinflammatory and anti-pyrexia effects might be related to the inflammatory pathway regulated by transient receptor potential.Additionally,QFZS treatment reduced transient receptor potential melastatin 2 ion channel expression and affected TNF-α,heat shock protein 70,and cyclooxygenase-2 expression in the hypothalamus.CONCLUSION:QFZS exerts its regulatory effects on fever by regulating the metabolism of lysophospholipids and arachidonic acid and the regulation of inflammation via transient receptor potential ion channels channels.展开更多
The Hodgkin–Huxley model assumes independent ion channel activation,although mutual interactions are common in biological systems.This raises the problem why neurons would favor independent over cooperative channel a...The Hodgkin–Huxley model assumes independent ion channel activation,although mutual interactions are common in biological systems.This raises the problem why neurons would favor independent over cooperative channel activation.In this study,we evaluate how cooperative activation of sodium channels affects the neuron’s information processing and energy consumption.Simulations of the stochastic Hodgkin–Huxley model with cooperative activation of sodium channels show that,while cooperative activation enhances neuronal information processing capacity,it greatly increases the neuron’s energy consumption.As a result,cooperative activation of sodium channel degrades the energy efficiency for neuronal information processing.This discovery improves our understanding of the design principles for neural systems,and may provide insights into future designs of the neuromorphic computing devices as well as systematic understanding of pathological mechanisms for neural diseases.展开更多
Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, tr...Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.展开更多
Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, ...Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes （TdP） like ventricular arrhythmia.^3 This may be due to the blockage on rectifier postassium current （Ik） of terfenadine, resulting in the prolongation of the action potential duration （APD） and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.^4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the lk and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.展开更多
Recent technical advances in electrophysiological measurements, organelle-targeted fluorescence imaging, and organelle proteomics have pushed the research of ion transport a step forward in the case of the plant bioen...Recent technical advances in electrophysiological measurements, organelle-targeted fluorescence imaging, and organelle proteomics have pushed the research of ion transport a step forward in the case of the plant bioenergetic organelles, chloroplasts and mitochondria, leading to the molecular identification and functional characterization of several ion transport systems in recent years. Here we focus on channels that mediate relatively high-rate ion and water flux and summarize the current knowledge in this field, focusing on targeting mechanisms, proteomics, electrophysiology, and physiological function. In addition, since chloroplasts evolved from a cyanobacterial ancestor, we give an overview of the information available about cyanobacterial ion channels and discuss the evolutionary origin of chloroplast channels. The recent molecular identification of some of these ion channels allowed their physiological functions to be studied using genetically modified Arabidopsis plants and cyanobacteria. The view is emerging that alteration of chloroplast and mitochondrial ion homeostasis leads to organelle dysfunction, which in turn significantly affects the energy metabolism of the whole organism. Clear-cut identification of genes encoding for chan- nels in these organelles, however, remains a major challenge in this rapidly developing field. Multiple stra- tegies including bioinformatics, cell biology, electrophysiology, use of organelle-targeted ion-sensitive probes, genetics, and identification of signals eliciting specific ion fluxes across organelle membranes should provide a better understanding of the physiological role of organellar channels and their contribution to signaling pathways in plants in the future.展开更多
Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have ...Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.Methods Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current （/Ca-L）,inward rectifier potassium current （/K1）, and transient outward potassium current （/to1） were studied in rat ventricular myocytes and sodium current （/Na）, slow delayed rectifier current （/Ks）, and HERG current （/Kr） were investigated in transfected human embryonic kidney 293 cells.Results One hundred μmol/L paeoniflorin reduced the peak /ca-L by 40.29% at the test potential of ±10 mV （from （-9.78±0.52） pA/pF to （-5.84±0.89） pA/pF, n=5, P=0.028）. The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were （-11.22±0.27） mV vs. （-5.95±0.84） mV （n=5,P=0.007）, respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred μmol/L paeoniflorin completely inhibited the peak /Na and the effect was reversible. Moreover,paeoniflorin inhibited the /K1 by 30.13% at the test potential of -100 mV （from （-25.26±8.21） pA/pF to （-17.65±6.52）pA/pF, n=6, F=0.015） without effects on the reversal potential and the rectification property. By contrast, 100 μmol/L paeoniflorin had no effects on/to1, /Ks or /Kr channels.Conclusions The study demonstrated that paeoniflorin blocked /Ca-L, /Na, and /Kf without affecting /to1, /Ks, or /Kr. The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.展开更多
The yolk–shell structure has a unique advantage in lithium-ion batteries applications due to its ability to effectively buffer the volume expansion of the lithiation/delithiation process.However,its development is li...The yolk–shell structure has a unique advantage in lithium-ion batteries applications due to its ability to effectively buffer the volume expansion of the lithiation/delithiation process.However,its development is limited by the low contact point between the core and shell.Herein,we propose a general strategy of simultaneous construction of sufficient reserved space and multicontinuous active channels by pyrolysis of two carbon substrates.A double-shell structure consisting of Co_(3)O_(4) anchored to hollow carbon sphere and external self-supporting zeolitic imidazolate framework(ZIF)layer was constructed by spray pyrolysis and additional carbon coating in-situ growth.In the process of high-temperature calcination,the carbon and nitrogen layers between the shells separate,creating additional space,while the Co_(3)O_(4) particles between the shells remain are still in close contact to form continuous and fast electron conduction channels,which can realize better charge transfer.Due to the synergy of these design principles,the material has ultra-high initial discharge capacities of 2,183.1 mAh·g^(−1) at 0.2 A·g^(−1) with capacity of 1,121.36 mAh·g^(−1) after 250 cycles,the long-term capacities retention rate is about 92.4%after 700 cycles at 1 A·g^(−1).This unique channel-type double-shell structure fights a way out to prepare novel electrode materials with high performance.展开更多
Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomoti...Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery （BA） of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows： （1） The diameters of BA and middle cerebral artery （MCA） were 314.5±15.7 μm （n=15） and 233.3±10.1 μm （n=12） at 10 mmHg working pressure （P〈0.05）, respectively. Pressure-induced vasomotion occurred in BA （22/28, 78.6%）, but not in MCA （4/31, 12.9%） from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; （2） The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic con- tractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 （n=13） per 10 min at 60 mmHg working pressure; （3） The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 181]-GA, TEA or in Ca2＋-free medium. Nifedipine, NFA, 18^-GA or Ca2＋-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results sug- gest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca2＋-activated C1- channels （CaCCs） currents and Kca currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells （VSMCs） to activate CaCCs. Depolarization in turn activates voltage-dependent Ca2＋ channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates Kca channels and hyperpo- larizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle.展开更多
The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid...The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.展开更多
Neuroscience has been extensively developed for more than seventy years;however,there still remains lack of breakthrough understanding in the neural information field.A quantum coherent state of ion channels is recent...Neuroscience has been extensively developed for more than seventy years;however,there still remains lack of breakthrough understanding in the neural information field.A quantum coherent state of ion channels is recently proposed in neural system as an information carrier,but its physical expression is still not fixed.Here,employing a simple K^(+)channel as a typical instance,we theoretically build a conceptual model for the quantum state of a neural ion channel and demonstrate the macroscopic coherence state of multiple ion channels.The underlying mechanism is revealed to the mid-infrared photons released by ion oscillation in one ion channel together with their resonant and coherent coupling with the oscillations in other channels.An additional environment field(e.g.,brain wave)may regulate the coherence,potentially relating to the human consciousness.Clearly,there exist the channels of other ions in a neural system,which also potentially form a macroscopic coherence state of themselves,with the mechanism identical to that of K^(+)channels.An environment field can be expected to further regulate the quantum states of various ionic channels,leading to a total macroscopic coherence state of these channels,which is like the conductor in a symphony to achieve the harmony in music.These findings are expected to provide a promising viewpoint for neuroscience,as well as to improve treatments of the diseases and health problems related to neural system.展开更多
OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Spra...OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.展开更多
Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^...Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.展开更多
This study describes methods for predicting and classifying voltage-gated ion channels. Firstly, a standard support vector machine （SVM） method was developed for predicting ion channels by using amino acid compositi...This study describes methods for predicting and classifying voltage-gated ion channels. Firstly, a standard support vector machine （SVM） method was developed for predicting ion channels by using amino acid composition and dipeptide composition, with an accuracy of 82.89% and 85.56%, respectively. The accuracy of this SVM method was improved from 85.56% to 89.11% when combined with PSIBLAST similarity search. Then we developed an SVM method for classifying ion channels （potassium, sodium, calcium, and chloride） by using dipeptide composition and achieved an overall accuracy of 96.89%. We further achieved a classification accuracy of 97.78% by using a hybrid method that combines dipeptidebased SVM and hidden Markov model methods. A web server VGIchan has been developed for predicting and classifying voltage-gated ion channels using the above approaches. VGIchan is freely available at www.imtech.res.in/raghava/vgichan/.展开更多
文摘Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.
文摘Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.
基金This work was supported by grants from the National Natural science Foundation of China （No. 81473199）, and the Fundamental Research Funds for the Central Universities （No, 015TS 125）.
文摘Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.
文摘Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of binding and fusionwith the oocyte. During capacitation various biochemical and biophysical changes occur in the spermatozoa and thespermatozoal membranes. Ions and ion channels also play important roles in governing the process of capacitation bychanging the fluxes of different ions which in turn controls various characteristics of capacitated spermatozoa. Alongwith the mobilization of ions the generation of free radicals and efflux of cholesterol also plays an important role in thecapacitation state of the spermatozoa. The generation of free radical and efflux of cholesterol change the mechano-dynamic properties of the membrane by oxidation of the polyunsaturated lipids and by generating the cholesterol freepatches. The process of capacitation renders the spermatozoa responsive to the inducers of the acrosome reaction. Theglycoprotein zona pellucida 3 (ZP3) of the egg coat zona pellucida is the potent physiological stimulator of the acro-some reaction; progesterone, a major compoent of the follicular fluid, is also an induce of the acrosome reaction.The inducers of the acrosome reaction cause the activation of the various ion-channels leading to high influxes of calci-um, sodium and bicarbonate. The efflux of cholesterol during the process of capacitation alters the permeablity of themembrane to the ions and generate areas which are prone to fusion and vesculation process during the acrosome reac-tion. Ths review focuses mainly on effects of the ion and ion-channels, free radicals, and membrane fluidity changesduring the process of capacitation and acrosome reaction. (Asian J Androl 1999 Sep; 1: 95-107)
基金supported by the National Natural Science Foundation of China,No.30872665
文摘Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2＋-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups： adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/I expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2＋ influx, inhibit calcium overload, and diminish Ca2＋ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.
文摘Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be ＂lethal＂, which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings： M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.
文摘The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly fully dehydrated ions, whereas only two of such binding sites exist in the non-selective NaK channel, and none of them is found in the NavAb sodium channel. Here we show that the stability of the selectivity filters in these tetrameric cation channels is inversely correlated with the number of stable binding sites by extensive molecular dynamics simulations. While the presence of coordinated ions is crucial for the selectivity filters of the KcsA and NaK channels to stabilize the conformations in their crystal structures, the selectivity filter of the NavAb channel shows higher stability, independent of the presence of ions. We further show that the distinct repulsive electrostatic interactions between negatively charged oxygen atoms in the selectivity filter which form the stable binding sites are responsible for the different stability of these cation channels. The hydrogen bonding networks between residues in the selectivity filter and its adjacent pore helix also play an important role in maintaining stability. Together, these results provide important mechanistic insights into the structural stability of the selectivity filters in typical cation channels.
基金Beijing Traditional Chinese Medicine Foundation for Science and Technology(JJ-2020-78):Research on the Protection of Intellectual Property Rights of Traditional Chinese MedicineScientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2021A00912):Basic and Translational Research on the Application of Traditional Chinese Medicine+1 种基金the Research Foundation of Major New Drug Creation,from the Ministry of Science and Technology of China(2018ZX09721003-009-022):Research on Key Technologies and Industrialization of Traditional Chinese Medicine Preparations for ChildrenNational Natural Science Foundation of China(82074060):Study on the Effect of Tanyu Tongzhi Fang in Maintaining Vascular Homeostasis in the Treatment of Atherosclerosis。
文摘OBJECTIVE:To explore how Qingfei Zhisou oral liquid(清肺止嗽口服液,QFZS)adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences.METHODS:Dry yeast was subcutaneously injected at 10 mL/kg to establish the pyrexia model.We randomly divided 60 Sprague-Dawley rats into five groups:control,model,positive,low dose of QFZS and high dose of QFZS.Inflammatory proteins were evaluated by Western blotting and immunohistochemistry.For the examination of the endogenous metabolites,enzyme linked immunosorbent assay and ultra-high-performance liquid chromatography high-resolution mass spectrometry were employed.RESULTS:QFZS significantly reduced rats'body temperature within 6 h after dry yeast injection and reduced the secretion of the arginine vasopressin,cyclic adenosine monophosphate,prostaglandin E-2,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1βin serum.Meanwhile,we identified 41 metabolites between the model and QFZS groups,including arachidonic acid and lysophospholipids.QFZS restored normal arachidonic acid levels.Based on the differential metabolite enrichment analysis,QFZS's antiinflammatory and anti-pyrexia effects might be related to the inflammatory pathway regulated by transient receptor potential.Additionally,QFZS treatment reduced transient receptor potential melastatin 2 ion channel expression and affected TNF-α,heat shock protein 70,and cyclooxygenase-2 expression in the hypothalamus.CONCLUSION:QFZS exerts its regulatory effects on fever by regulating the metabolism of lysophospholipids and arachidonic acid and the regulation of inflammation via transient receptor potential ion channels channels.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.lzujbky-2021-62)the Shanghai Municipal Science and Technology Major Project(Grant No.2018SHZDZX01)Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(LCNBI)and ZJLab,and the National Natural Science Foundation of China(Grant No.12247101).
文摘The Hodgkin–Huxley model assumes independent ion channel activation,although mutual interactions are common in biological systems.This raises the problem why neurons would favor independent over cooperative channel activation.In this study,we evaluate how cooperative activation of sodium channels affects the neuron’s information processing and energy consumption.Simulations of the stochastic Hodgkin–Huxley model with cooperative activation of sodium channels show that,while cooperative activation enhances neuronal information processing capacity,it greatly increases the neuron’s energy consumption.As a result,cooperative activation of sodium channel degrades the energy efficiency for neuronal information processing.This discovery improves our understanding of the design principles for neural systems,and may provide insights into future designs of the neuromorphic computing devices as well as systematic understanding of pathological mechanisms for neural diseases.
文摘Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.
基金This study was supported by a grant from Education Government Foundation of Shanxi Province, China(No. 2003105).
文摘Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes （TdP） like ventricular arrhythmia.^3 This may be due to the blockage on rectifier postassium current （Ik） of terfenadine, resulting in the prolongation of the action potential duration （APD） and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.^4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the lk and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.
文摘Recent technical advances in electrophysiological measurements, organelle-targeted fluorescence imaging, and organelle proteomics have pushed the research of ion transport a step forward in the case of the plant bioenergetic organelles, chloroplasts and mitochondria, leading to the molecular identification and functional characterization of several ion transport systems in recent years. Here we focus on channels that mediate relatively high-rate ion and water flux and summarize the current knowledge in this field, focusing on targeting mechanisms, proteomics, electrophysiology, and physiological function. In addition, since chloroplasts evolved from a cyanobacterial ancestor, we give an overview of the information available about cyanobacterial ion channels and discuss the evolutionary origin of chloroplast channels. The recent molecular identification of some of these ion channels allowed their physiological functions to be studied using genetically modified Arabidopsis plants and cyanobacteria. The view is emerging that alteration of chloroplast and mitochondrial ion homeostasis leads to organelle dysfunction, which in turn significantly affects the energy metabolism of the whole organism. Clear-cut identification of genes encoding for chan- nels in these organelles, however, remains a major challenge in this rapidly developing field. Multiple stra- tegies including bioinformatics, cell biology, electrophysiology, use of organelle-targeted ion-sensitive probes, genetics, and identification of signals eliciting specific ion fluxes across organelle membranes should provide a better understanding of the physiological role of organellar channels and their contribution to signaling pathways in plants in the future.
文摘Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.Methods Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current （/Ca-L）,inward rectifier potassium current （/K1）, and transient outward potassium current （/to1） were studied in rat ventricular myocytes and sodium current （/Na）, slow delayed rectifier current （/Ks）, and HERG current （/Kr） were investigated in transfected human embryonic kidney 293 cells.Results One hundred μmol/L paeoniflorin reduced the peak /ca-L by 40.29% at the test potential of ±10 mV （from （-9.78±0.52） pA/pF to （-5.84±0.89） pA/pF, n=5, P=0.028）. The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were （-11.22±0.27） mV vs. （-5.95±0.84） mV （n=5,P=0.007）, respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred μmol/L paeoniflorin completely inhibited the peak /Na and the effect was reversible. Moreover,paeoniflorin inhibited the /K1 by 30.13% at the test potential of -100 mV （from （-25.26±8.21） pA/pF to （-17.65±6.52）pA/pF, n=6, F=0.015） without effects on the reversal potential and the rectification property. By contrast, 100 μmol/L paeoniflorin had no effects on/to1, /Ks or /Kr channels.Conclusions The study demonstrated that paeoniflorin blocked /Ca-L, /Na, and /Kf without affecting /to1, /Ks, or /Kr. The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.
基金supported by the National Natural Science Foundation of China(Nos.21871005 and 22171005)the Program for Innovative Research Team of Anhui Education Committee,the Project for Collaborative Innovation of Anhui Higher Education Institutes(Nos.GXXT-2020-005,GXXT-2021-012,and GXXT-2021-013)+1 种基金the Natural Science Foundation of the Education Department of Anhui Province(No.KJ2020A0075)the Foundation of the Anhui Province Key Laboratory of Clean Energy Materials and Chemistry for Sustainable Conversion of Natural Resources(No.LCECSC-10).
文摘The yolk–shell structure has a unique advantage in lithium-ion batteries applications due to its ability to effectively buffer the volume expansion of the lithiation/delithiation process.However,its development is limited by the low contact point between the core and shell.Herein,we propose a general strategy of simultaneous construction of sufficient reserved space and multicontinuous active channels by pyrolysis of two carbon substrates.A double-shell structure consisting of Co_(3)O_(4) anchored to hollow carbon sphere and external self-supporting zeolitic imidazolate framework(ZIF)layer was constructed by spray pyrolysis and additional carbon coating in-situ growth.In the process of high-temperature calcination,the carbon and nitrogen layers between the shells separate,creating additional space,while the Co_(3)O_(4) particles between the shells remain are still in close contact to form continuous and fast electron conduction channels,which can realize better charge transfer.Due to the synergy of these design principles,the material has ultra-high initial discharge capacities of 2,183.1 mAh·g^(−1) at 0.2 A·g^(−1) with capacity of 1,121.36 mAh·g^(−1) after 250 cycles,the long-term capacities retention rate is about 92.4%after 700 cycles at 1 A·g^(−1).This unique channel-type double-shell structure fights a way out to prepare novel electrode materials with high performance.
基金supported by grants from National Basic Research Program of China(No.2012CB52660000)National Natural Science Foundation of China(No.81000411,No.31100829,and No.31260247)
文摘Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery （BA） of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows： （1） The diameters of BA and middle cerebral artery （MCA） were 314.5±15.7 μm （n=15） and 233.3±10.1 μm （n=12） at 10 mmHg working pressure （P〈0.05）, respectively. Pressure-induced vasomotion occurred in BA （22/28, 78.6%）, but not in MCA （4/31, 12.9%） from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; （2） The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic con- tractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 （n=13） per 10 min at 60 mmHg working pressure; （3） The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 181]-GA, TEA or in Ca2＋-free medium. Nifedipine, NFA, 18^-GA or Ca2＋-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results sug- gest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca2＋-activated C1- channels （CaCCs） currents and Kca currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells （VSMCs） to activate CaCCs. Depolarization in turn activates voltage-dependent Ca2＋ channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates Kca channels and hyperpo- larizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle.
基金supported by the Department of Science and Technology-Cognitive Science Initiative project funded to Sushil K Jhasupport from Department of Biotechnology (DBT), Department of Science and Technology(PURSE), Universities for Potential of Excellence (UPOE Ⅱ) and University Grants Commission-Special Assistance Programme)JNU funds to Sushil K Jha。
文摘The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.
基金supported by the National Key Research and Development Program of China(2018YFE0205501)the National Natural Science Foundation of China Project(21988102)the National Supercomputer Center in Tianjin。
文摘Neuroscience has been extensively developed for more than seventy years;however,there still remains lack of breakthrough understanding in the neural information field.A quantum coherent state of ion channels is recently proposed in neural system as an information carrier,but its physical expression is still not fixed.Here,employing a simple K^(+)channel as a typical instance,we theoretically build a conceptual model for the quantum state of a neural ion channel and demonstrate the macroscopic coherence state of multiple ion channels.The underlying mechanism is revealed to the mid-infrared photons released by ion oscillation in one ion channel together with their resonant and coherent coupling with the oscillations in other channels.An additional environment field(e.g.,brain wave)may regulate the coherence,potentially relating to the human consciousness.Clearly,there exist the channels of other ions in a neural system,which also potentially form a macroscopic coherence state of themselves,with the mechanism identical to that of K^(+)channels.An environment field can be expected to further regulate the quantum states of various ionic channels,leading to a total macroscopic coherence state of these channels,which is like the conductor in a symphony to achieve the harmony in music.These findings are expected to provide a promising viewpoint for neuroscience,as well as to improve treatments of the diseases and health problems related to neural system.
基金Supported by National Essence Basic Research and Development 973 Program(the Effects of Meridian Specific Target Organ Response to Biological Basic Research,No.2012CB518503)
文摘OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.
基金supported by the National Natural Science Foundation of China,No.82173800 (to JB)Shenzhen Science and Technology Program,No.KQTD20200820113040070 (to JB)。
文摘Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.
文摘This study describes methods for predicting and classifying voltage-gated ion channels. Firstly, a standard support vector machine （SVM） method was developed for predicting ion channels by using amino acid composition and dipeptide composition, with an accuracy of 82.89% and 85.56%, respectively. The accuracy of this SVM method was improved from 85.56% to 89.11% when combined with PSIBLAST similarity search. Then we developed an SVM method for classifying ion channels （potassium, sodium, calcium, and chloride） by using dipeptide composition and achieved an overall accuracy of 96.89%. We further achieved a classification accuracy of 97.78% by using a hybrid method that combines dipeptidebased SVM and hidden Markov model methods. A web server VGIchan has been developed for predicting and classifying voltage-gated ion channels using the above approaches. VGIchan is freely available at www.imtech.res.in/raghava/vgichan/.
