Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on t...Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current （Ito） and slow delayed rectifier potassium current （IKs）. Methods The monophasic action potential （MAP） technique was used to record the MAP duration of the epicardium （Epi）, myocardium （M） and endocardium （Endo） of the rabbit heart and the whole cell patch clamp was used to record/to and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization （TDR） in rabbit transmural ventricular wall. ALL decreased the current densities of/to and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation ofIto in M layers and partly inhibit the channel openings of/to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of tmnsmural inhibition of/to and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.展开更多
The effects of protein kinase C （PKC） on the tension and the activity of voltage-dependent delayed rectifier potassium channel （K,,） were examined in normal and passively sensitized human airway smooth muscle （H...The effects of protein kinase C （PKC） on the tension and the activity of voltage-dependent delayed rectifier potassium channel （K,,） were examined in normal and passively sensitized human airway smooth muscle （HASM）, by measuring tones and whole-cell patch clamp techniques, and the Kv activities and membrane potential （Em） were also detected. The results showed that phorbol 12-myristate 13-acetate （PMA）, a PKC activator, caused a concentration-dependent constriction in normal HASM rings. The constriction of the passively sensitized muscle in asthma serum group was significantly higher than that of the normal group （P〈0.05）, and the constrictions of both groups were completely abolished by PKC inhibitor Ro31-8220 and calcium channel inhibitor nifedipine. Kv activities of HASM cells were significantly inhibited by PMA, and the Em became more positive, as compared with the DMSO （a PMA menstruum）-treated group （P〈0.01）. This effect could be blocked by Ro31-8220 （P〈0.01 ）. It was concluded that activation of PKC could increase the tones of HASM, which might be related to the reduced Kv activity. In passively sensitized HASM rings, this effect was more notable.展开更多
Background Potassium (K +) channels are important in regulating cell membrane potential and excitability. Although bronchial myocytes from asthmatic rats show a significant reduction in voltage-dependent delayed rec...Background Potassium (K +) channels are important in regulating cell membrane potential and excitability. Although bronchial myocytes from asthmatic rats show a significant reduction in voltage-dependent delayed rectifier potassium channel (Kv) current density and higher excitability, the activity and expression of Kv in human bronchial smooth muscle cells (HBSMCs) have never been studied. The ob jective of this study was to investigate the effect of passive sensitization by asthmatic serum on the activity of Kv and the expression of Kv isoform Kv1.5 in HBSMCs.Methods HBSMCs were randomly divided into two groups: control group (containing 10% serum from nonatopic individuals) and sensitized group (containing 10% asthmatic serum), then cultured for 24 hours. Whole-cell patch clamp, immunofluorescence staining, reverse transcription-polymerase chain reaction and Western blot techniques were used to study the effect of passive sensitization on the activity of Kv and the expression of Kv1.5 in HBSMCs.Results The membrane potential in passively sensitized HBSMCs was significantly depolarized to -(26.7±5.2) mV compared with -(41.3±6.4) mV in the cont rol group (P<0.01). Passive sensitization caused a significant inhibition of Kv currents in HBSMCs, resulting in a downward shift in the current-voltage (Ⅰ-Ⅴ) relationship curve. At +50mV, the peak Kv current density of passively sensitized HBSMCs was significantly decreased from (54.6±8.7) picoamperes per picofarad ( pA/pF) to (32.1±7.1) pA/pF (P<0.01). The expression level of Kv1.5 mRNA in passively sensitized HBSMCs was significantly lower than that in the control group (0.76±0.07 vs 1.04±0.13, P<0.05). The expression of Kv1.5 protein of passively sensitized HBSMCs was also significantly reduced compared to that from the control group (984±168 vs 2200±380, P<0.05).Conclusions The activity and expression of Kv were all decreased in HBSMCs passively sensitized by asthmatic serum compared with nonsensitized cells. These changes might be involved in the mechanisms of formation and development of asthma.展开更多
Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, ...Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig myocytes using the whole cell configuration of the patch clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may result in its supperior antiarrhythmic efficacy compared to d sotalol.展开更多
Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic s...Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.展开更多
To investigate the effect of intedeukin-1β （IL-1β） on IA and IK currents in cultured murine trigeminal ganglion （TG） neurons, whole-cell patch clamp technique was used to record the IA and IK currents before and...To investigate the effect of intedeukin-1β （IL-1β） on IA and IK currents in cultured murine trigeminal ganglion （TG） neurons, whole-cell patch clamp technique was used to record the IA and IK currents before and after 20 ng/mL IL-1β perfusion. Our results showed that 20 ng/mL IL-1β inhibited IA currents （18.3±10.7）% （n=6, P〈0.05）. IL-1β at 20 ng/mL had no effect on G-V curve of IA but moved the H-infinity curve V0.5 from -36.6±6. 1 mV to-42.4±5.2 mV （n=5, P〈0.01）. However, 20 ng/mL IL-1β had effect on neither the amplitude nor the G-V curve of IK. IL-1β was found to selectively inhibit IA current in TG neurons and the effect may contribute to hyperalgesia under various inflammatory conditions.展开更多
Background:Stellate ganglion(SG)plays an important role in cardiovascular diseases.The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system.The aim of this research was to ev...Background:Stellate ganglion(SG)plays an important role in cardiovascular diseases.The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system.The aim of this research was to evaluate the effects offluvastatin on the electrophysiological characteristics of SG neurons in a rabbit model of myocardial ischemia(MI).Methods:The MI model was induced by abdominal subcutaneous injections of isoproterenol in rabbits.Using whole-cell patch clamp technique,we studied the characteristic changes of ion channels and action potentials(APs)in isolated SG neurons in control group(n=20),MI group(n=20)and fluvastatin pretreated group(fluvastatin group,n=20),respectively.The protein expression of sodium channel in SG was determined by immunohistochemical analysis.Results:MI and the intervention of fluvastatin did not have significantly influence on the characteristics of delayed rectifier potassium channel currents.The maximal peak current density of sodium channel currents in SG neurons along with the characteristics of activation curves,inactivation curves,and recovery curves after inactivation were changed in the MI group.The peak current densities of control group,MI group,and fluvastatin group(n=10 in each group)were-71.77±23.22 pA/pF,-126.75±18.90 pA/pF,and-86.42±28.30 pA/pF,respectively(F=4.862,P=0.008).Fluvastatin can decrease the current amplitude which has been increased by MI.Moreover,fluvastatin induced the inactivation curves and post-inactive recovery curves moving to the position of the control group.But the expression of sodium channel-associated protein(Nav 1.7)had no significantly statistical difference among the three groups.The percentages of Nav 1.7 protein in control group,MI group,and fluvastatin group(n=5 in each group)were 21.49±7.33%,28.53±8.26%,and 21.64±2.78%,respectively(F=1.495,P=0.275).Moreover,MI reduced the electrical activity of AP and increased amplitude of AP,fluvastatin pretreatment could recover amplitude and electrical activity of AP.The probability of neurons induced continuous APs were 44.44%,14.29%,and 28.57%in control group,MI group,and fluvastatin group,respectively.Conclusions:Fluvastatin pretreatment can recover electrophysiology characteristics of ion channel and AP in SG neurons in a rabbit model of MI.It could be considered as potential method for treating coronary heart diseases.展开更多
Using the whole cell patch clamp technique, the effect of Cu^2＋on transient outward K^＋current （/to） and delayed rectifier K^＋ current （Idr） was studied in acutely isolated rat hippocampal neurons.Ito and Idr w...Using the whole cell patch clamp technique, the effect of Cu^2＋on transient outward K^＋current （/to） and delayed rectifier K^＋ current （Idr） was studied in acutely isolated rat hippocampal neurons.Ito and Idr were increased when the concentration of Cu^2＋ was lower than 2 × 10^-5 and 10^-5 tool/L, respectively, and increased ratio was decreased with increasing Cu^2＋concentration in the bath solutions. When the concentration continued to increase to 5× 10^-5 and 2 × 10^- 5 mol/L, the currents were hardly changed, while the concentration was more than 10^-4 and 5 × 10^-5 mol/L, the currents were inhibited remarkably. Cu^2＋ （10^-5 mol/L） did not affect the activation and inactivation process of Ito. The activation curve of Idr was shifted toward positive potential, but 10^-5 mol/L Cu^2＋did not affect slope factor. According to these results, it was considered that Cu^2＋at low concentration in the bath solution could promote Ito and Idr while at high concentration could inhibit them, and change of amplitude was different with different membrane voltage. Conclusion was drawn： Cu^2＋may be involved in the pathophysiologic mechanism of diseases with neuropathological components.展开更多
文摘Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current （Ito） and slow delayed rectifier potassium current （IKs）. Methods The monophasic action potential （MAP） technique was used to record the MAP duration of the epicardium （Epi）, myocardium （M） and endocardium （Endo） of the rabbit heart and the whole cell patch clamp was used to record/to and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization （TDR） in rabbit transmural ventricular wall. ALL decreased the current densities of/to and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation ofIto in M layers and partly inhibit the channel openings of/to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of tmnsmural inhibition of/to and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.
基金This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30270583)
文摘The effects of protein kinase C （PKC） on the tension and the activity of voltage-dependent delayed rectifier potassium channel （K,,） were examined in normal and passively sensitized human airway smooth muscle （HASM）, by measuring tones and whole-cell patch clamp techniques, and the Kv activities and membrane potential （Em） were also detected. The results showed that phorbol 12-myristate 13-acetate （PMA）, a PKC activator, caused a concentration-dependent constriction in normal HASM rings. The constriction of the passively sensitized muscle in asthma serum group was significantly higher than that of the normal group （P〈0.05）, and the constrictions of both groups were completely abolished by PKC inhibitor Ro31-8220 and calcium channel inhibitor nifedipine. Kv activities of HASM cells were significantly inhibited by PMA, and the Em became more positive, as compared with the DMSO （a PMA menstruum）-treated group （P〈0.01）. This effect could be blocked by Ro31-8220 （P〈0.01 ）. It was concluded that activation of PKC could increase the tones of HASM, which might be related to the reduced Kv activity. In passively sensitized HASM rings, this effect was more notable.
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 3 0 2 70 5 83 )
文摘Background Potassium (K +) channels are important in regulating cell membrane potential and excitability. Although bronchial myocytes from asthmatic rats show a significant reduction in voltage-dependent delayed rectifier potassium channel (Kv) current density and higher excitability, the activity and expression of Kv in human bronchial smooth muscle cells (HBSMCs) have never been studied. The ob jective of this study was to investigate the effect of passive sensitization by asthmatic serum on the activity of Kv and the expression of Kv isoform Kv1.5 in HBSMCs.Methods HBSMCs were randomly divided into two groups: control group (containing 10% serum from nonatopic individuals) and sensitized group (containing 10% asthmatic serum), then cultured for 24 hours. Whole-cell patch clamp, immunofluorescence staining, reverse transcription-polymerase chain reaction and Western blot techniques were used to study the effect of passive sensitization on the activity of Kv and the expression of Kv1.5 in HBSMCs.Results The membrane potential in passively sensitized HBSMCs was significantly depolarized to -(26.7±5.2) mV compared with -(41.3±6.4) mV in the cont rol group (P<0.01). Passive sensitization caused a significant inhibition of Kv currents in HBSMCs, resulting in a downward shift in the current-voltage (Ⅰ-Ⅴ) relationship curve. At +50mV, the peak Kv current density of passively sensitized HBSMCs was significantly decreased from (54.6±8.7) picoamperes per picofarad ( pA/pF) to (32.1±7.1) pA/pF (P<0.01). The expression level of Kv1.5 mRNA in passively sensitized HBSMCs was significantly lower than that in the control group (0.76±0.07 vs 1.04±0.13, P<0.05). The expression of Kv1.5 protein of passively sensitized HBSMCs was also significantly reduced compared to that from the control group (984±168 vs 2200±380, P<0.05).Conclusions The activity and expression of Kv were all decreased in HBSMCs passively sensitized by asthmatic serum compared with nonsensitized cells. These changes might be involved in the mechanisms of formation and development of asthma.
文摘Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig myocytes using the whole cell configuration of the patch clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may result in its supperior antiarrhythmic efficacy compared to d sotalol.
基金grants obtained from the National Natural Science Foundation of China （No.： 81170177, 81030002） and science and Technology De- partment of Gansu Province Project （145RJZ104）.
文摘Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.
基金The project was supported by a grant from the National Natural Sciences Foundation of China (No. 30271500)
文摘To investigate the effect of intedeukin-1β （IL-1β） on IA and IK currents in cultured murine trigeminal ganglion （TG） neurons, whole-cell patch clamp technique was used to record the IA and IK currents before and after 20 ng/mL IL-1β perfusion. Our results showed that 20 ng/mL IL-1β inhibited IA currents （18.3±10.7）% （n=6, P〈0.05）. IL-1β at 20 ng/mL had no effect on G-V curve of IA but moved the H-infinity curve V0.5 from -36.6±6. 1 mV to-42.4±5.2 mV （n=5, P〈0.01）. However, 20 ng/mL IL-1β had effect on neither the amplitude nor the G-V curve of IK. IL-1β was found to selectively inhibit IA current in TG neurons and the effect may contribute to hyperalgesia under various inflammatory conditions.
文摘Background:Stellate ganglion(SG)plays an important role in cardiovascular diseases.The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system.The aim of this research was to evaluate the effects offluvastatin on the electrophysiological characteristics of SG neurons in a rabbit model of myocardial ischemia(MI).Methods:The MI model was induced by abdominal subcutaneous injections of isoproterenol in rabbits.Using whole-cell patch clamp technique,we studied the characteristic changes of ion channels and action potentials(APs)in isolated SG neurons in control group(n=20),MI group(n=20)and fluvastatin pretreated group(fluvastatin group,n=20),respectively.The protein expression of sodium channel in SG was determined by immunohistochemical analysis.Results:MI and the intervention of fluvastatin did not have significantly influence on the characteristics of delayed rectifier potassium channel currents.The maximal peak current density of sodium channel currents in SG neurons along with the characteristics of activation curves,inactivation curves,and recovery curves after inactivation were changed in the MI group.The peak current densities of control group,MI group,and fluvastatin group(n=10 in each group)were-71.77±23.22 pA/pF,-126.75±18.90 pA/pF,and-86.42±28.30 pA/pF,respectively(F=4.862,P=0.008).Fluvastatin can decrease the current amplitude which has been increased by MI.Moreover,fluvastatin induced the inactivation curves and post-inactive recovery curves moving to the position of the control group.But the expression of sodium channel-associated protein(Nav 1.7)had no significantly statistical difference among the three groups.The percentages of Nav 1.7 protein in control group,MI group,and fluvastatin group(n=5 in each group)were 21.49±7.33%,28.53±8.26%,and 21.64±2.78%,respectively(F=1.495,P=0.275).Moreover,MI reduced the electrical activity of AP and increased amplitude of AP,fluvastatin pretreatment could recover amplitude and electrical activity of AP.The probability of neurons induced continuous APs were 44.44%,14.29%,and 28.57%in control group,MI group,and fluvastatin group,respectively.Conclusions:Fluvastatin pretreatment can recover electrophysiology characteristics of ion channel and AP in SG neurons in a rabbit model of MI.It could be considered as potential method for treating coronary heart diseases.
基金Project supported by the National Natural Science Foundation of China （No. 30470408）.
文摘Using the whole cell patch clamp technique, the effect of Cu^2＋on transient outward K^＋current （/to） and delayed rectifier K^＋ current （Idr） was studied in acutely isolated rat hippocampal neurons.Ito and Idr were increased when the concentration of Cu^2＋ was lower than 2 × 10^-5 and 10^-5 tool/L, respectively, and increased ratio was decreased with increasing Cu^2＋concentration in the bath solutions. When the concentration continued to increase to 5× 10^-5 and 2 × 10^- 5 mol/L, the currents were hardly changed, while the concentration was more than 10^-4 and 5 × 10^-5 mol/L, the currents were inhibited remarkably. Cu^2＋ （10^-5 mol/L） did not affect the activation and inactivation process of Ito. The activation curve of Idr was shifted toward positive potential, but 10^-5 mol/L Cu^2＋did not affect slope factor. According to these results, it was considered that Cu^2＋at low concentration in the bath solution could promote Ito and Idr while at high concentration could inhibit them, and change of amplitude was different with different membrane voltage. Conclusion was drawn： Cu^2＋may be involved in the pathophysiologic mechanism of diseases with neuropathological components.
