Alteration of transient outward potassium current in ventricular myocytes from 1-week and 2-month infarcted rabbit hearts

AIM: To study the current density of transient outward potassium current (I_to) in cells from the epicardial zone of the 1-week and 2-month infarcted rabbit heart. METHODS: Rabbits were infarcted by ligation of the left anterior descending coronary artery, 1 week as well as 2 months later, the single ventricular myocytes were isolated enzymatically from the infracted area of 1-week infracted rabbit heart (PMI-1 week) and 2-month infracted heart (PMI-2 months), region remote from the infracted zone of 2-month infracted heart (REM-2 months) and free wall of left ventricule from noninfarcted heart (CON). I_to was recorded using whole cell patch-clamp techniques. RESULTS: Membrane capacitance of myocytes in REM-2 months group was signifitantly larger than that in CON. I_tocurrent density (at +60 mV) was significantly reduced in PMI-1 week and PMI-2 months compared with CON , P＜0.01. Nevertheless, there was an significant increase in PMI-2M compared with PMI-1W, P＜0.05. I_to current density was also significantly decreased in REM-2 months compared with CON (P＜0.05), while there was an significant increase in REM-2 months compared with PMI-2 months, P＜0.05. CONCLUSION: The results indicated that the reduction and change of I_to in infarcted rabbit heart were heterogenous. These changes may underlie the abnormally long transmembrane action potentials of these arrhymogenic surviving ventricular fibers of the infarcted heart, thus contributing to reentrant arrhythmias in the infarcted heart. By 2 months after myocardial infarction, the depressed I_to of infracted area had returned to nearly normal, suggesting the presence of reverse remodeling.     

Characteristics of transient outward potassium current in repolarization 1 phase from the canine right ventricular mid-myocardial cells

AIM: To examine the electrophysiological characteristics of transient outward potassium current(Ito₁) in repolarization 1 phase from the canine right ventricular M cells. METHODS: By use of whole cell patch-clamp technique, we quantitatively researched the ionic intensity, density of Ito₁ and the notch magnitude of action potential in repolarization 1 phase. RESULTS: (1) The activating process of Ito₁ of canine right ventricular M cells presented evident voltage-dependency. Under the condition of 37℃, 5 000 ms, 0 mV and +70 mV, the average peak Ito₁ intensity of right ventricular M cell were (690±380) pA and (3 130±1 910) pA, respectively (P＜0.01). (2) The Ito₁ intensity of canine right ventricular M cell possessed obvious frequent dependency. Under the condition of 37℃,+70 mV, 500 ms and 5 000 ms, the average peak Ito₁ intensity were (1 690±830) pA,(3 130±1 910) pA, respectively(P＜0.01), corresponding to the increase of action potential "spike-dome" magnitude in repolarization 1 phase. CONCLUSION: Potent Ito₁ as well as the "spike-dome"-like action potential figure mediated by Ito₁ is one of the prominent electrophysiological characteristics of the canine right ventricular M cells.     

Effects of stretch on transient outward potassium and inward rectifier potassium current in cultured neonatal rat atrial myocytes

AIM：To investigate the effects of mechanical stretch on transient outward potassium current (Ito), inward rectifier potassium current (IK1) and action potential duration(APD) of cultured neonatal rat atrial myocytes. METHODS：Neonatal rat atrial myocytes were isolated and cultured on silicone sheeting with or without stretch for 24 h. The silicone membrane area was increased by 12% in stretched group. The cells without stretch served as control. Ito, IK1 and APD were recorded by the technique of whole-cell patch clamp. RESULTS：Compared with control group, Ito density in stretched myocytes was significantly reduced ［(16±04) pA/pF vs (121±29) pA/pF, P<001］, whereas IK1 density was increased ［(-108±08) pA/pF vs (-88±09) pA/pF, P<001］. The APDs at 50% and 90% levels of repolarization (APD50 and APD90) in the stretched cells were obviously decreased than those in non-stretched cells ［(105±14) ms vs (155±24) ms, (300±28) ms vs (563±36) ms, P<001］. CONCLUSION：Stretch stimulation leads to the reduction of Ito density, the increase in IK1 density and the shortness of APD in cultured rat atrial neonatal myocytes, which may contribute to atrial electrical remodeling induced by pressure overload.     

Effect of hypercholesterolemia on the ionic currents in cardiac ventricular myocytes of rats

AIM: To determine whether chronic hypercholesterolemia affects ionic currents on cardiac ventricular myocytes of rats. METHODS: Whole-cell patch-clamp technique was used to record the ionic currents in single cardiac myocytes isolated from normal cholesterolemia and hypercholesterolemia rats. RESULTS: In the hypercholesterol group (group Ⅱ), serum total-cholesterol level was significantly higher than that of normal group (group Ⅰ) ［(3.10±0.62)mmol·L-1 vs (1.18±0.37)mmol·L-1, P<0.01, n=20］. The serum triglyceride content of group II was remarkably higher than that of group Ⅰ ［(1.51±0.30)mmol·L-1 vs (0.43±0.15)mmol·L-1, P<0.01, n=20］. In ventricular myocytes of rats, 50% repolarization of action potential duration (APD50) prolonged from (70.86±8.12)ms (group Ⅰ) to (116.16±6.90)ms (group Ⅱ) (n=10 in each group, P<0.01); APD90 prolonged from (95.10±7.27)ms (group Ⅰ) to (144.04±7.39)ms (group Ⅱ) (n=10 in each group, P<0.01); at the test potential of -120 mV, Ik1 increased from (-16.98±4.54) pA/pF(group Ⅰ) to (-19.92±4.08) pA/pF (group Ⅱ) (n=12 in each group, P<0.05); at the test potential of 0 mV, ICa-L decreased from (-8.56±1.29) pA/pF (group Ⅰ) to (-5.24±0.90) pA/pF (group Ⅱ) (n=10 in each group, P<0.01); at the test potential of +60 mV, Ito decreased from (13.20±1.97) pA/pF (group Ⅰ) to (10.30±1.97) pA/pF (group Ⅱ) (n=8 in each group, P<0.05). CONCLUSION: Hypercholesterolemia affects the ionic currents on cardiomyocytes of rats greatly, which may be the ionic mechanism of cardiac toxicity induced by hypercholesterolemia.     

Downregulated transient outward potassium channel protein Kv4.2 and Kv4.3 expression in PVN contributes to sympathoexcitation in rats with chronic heart failure

AIM: To investigate the transient outward potassium channel protein expression in paraventricular nucleus(PVN) and its contribution to renal sympathetic nerve activity(RSNA) in rats with chronic heart failure(CHF).METHODS: A rat model of CHF was prepared by acute myocardial infarction that was induced by ligation of the left anterior descending coronary artery. Four weeks after heart failure, echocardiogram was applied to identify the CHF model and plasma norepinephrine(NE), serum NH₂-terminal pro-brain natriuretic peptide(NT-proBNP) were detected by ELISA. The expression of ransient outward potassium channel proteins Kv4.2 and Kv4.3 at mRNA and protein levels was determined by real-time PCR and Western blot. The mean arterial pressure(MAP), heart rate(HR) and RSNA were measured in anesthetized rats with PVN microinjection of potassium channel blockers 4-AP. RESULTS: In CHF group, the rat cardiac function and Kv4.2 and Kv4.3 expression in PVN were obviously lower while plasma NE and serum NT-proBNP were obviously higher than those in sham group. Microinjection of 4-AP into PVN induced an increase in MAP, HR and RSNA in both sham and CHF rats, while the CHF rats exhibited smaller responses to 4-AP than sham-operated rats.CONCLUSION: Downregulation of Kv4.2 and Kv4.3 expression in the PVN may be a potential mechanism for sympathoexciation in the rats with chronic heart failure.     

Effects of apelin-13 on transient sodium currents in rat ischemic ventricular myocardial cells

AIM：To investigate the effects of apelin on ventricular arrythmias and cardiac functions in rat Langendorff perfusion-simulated myocardial ischemia model by observing the changes of transient sodium currents (INa) in normal cells and the simulated ischemic cells in rat left ventricle. METHODS：Ventricular cells were enzymatically isolated by the Langendorff perfusion system. INa was recorded by the technique of whole-cell patch-clamp. Some elements in the extracellular fluid were changed to simulate the normal or ischemic status. Forty Wistar rats were divided into 4 groups：normal group, ischemic group, normal with apelin group and ischemic with apelin group. The effect of apelin-13 on INa was observed. The method of rat Langendorff perfusion was used to simulate the ischemic heart model. The ventricular arrhythmia scores and heart functional parameters were compared. The expression level of sodium channel protein,type V,alpha subunit (SCN5A) in ventricular ischemic cells was measured by Western blotting. RESULTS： Apelin-13 increased INa amplitude in both normal myocardial cells ［(-86±13） pA/pF］ and ischemic myocardial cells ［(-52±15） pA/pF］. The results of current-voltage curve analysis indicated that apelin-13 did not change the conduction velocity of INa in the 4 groups ［(3.2±0.2） pS/pF, （3.1±0.3） pS/pF,（2.9±0.1）pS/pF and （2.8±0.4） pS/pF,respectively, P>0.05］. The membrane potentials at 50% maximal activation in the 4 groups were （-21.9±0.6） mV, （-28.7±0.3） mV, （-30.5±0.7） mV and （-36.8±0.2） mV, respectively, and the slope of activation curves was 5.6±0.3, 5.1±0.4, 4.3±0.3 and 4.9±0.6 (P>0.05), respectively. No difference of ventricular arrhythmia scores between normal group and normal with apelin group, as well as between ischemic group and ischemic with apelin group was observed. LVEDP in normal with apelin group was lower than that in normal group.The dp/dtmax and dp/dtmin in normal with apelin group were higher than those in normal group. Apelin improved cardiac function parameters in the ischemic hearts. The expression of SCN5A was not affected by apelin (28.8±3.6, 29.4±4.1, 30.1±2.9 and 31.3±3.8,respectively,P>0.05). CONCLUSION：Apelin-13 changes the gating properties of sodium channel, enhances the peak INa and facilitates the opening of sodium channel without inducing ventricular arrhythmias. Apelin-13 has a positive inotropic effect on both normal and ischemic hearts.     

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AIM: To study the effect of panax notoginseng sponins (PNS) on L-type Ca²⁺ current in isolated right ventricle myocytes from chronic hypoxic rats. METHODS: Using whole cell patch clamp recording technique,we measured I_Ca-L in isolated right ventricle myocytes which were divided into three group:control group, chronic hy-poxic group and chronic hypoxic group with PNS(100 mg·kg^-1·d^-1). RESULTS: The result showed I_Ca-L of cells from chronic hypoxic group were significantly larger than the other two groups(P＜0.05). CONCLUSION: PNS decreases L-type Ca²⁺ current of the right ventricle myocytes from chronic hypoxic rats.     

Effect of platelet activating factor on the action potential and potassium currents in guinea-pig ventricular myocytes

AIM: To investigate the effects of platelet activating factor (PAF) on the action potential and potassium currents in guinea-pig ventricular myocytes. METHODS: By using whole-cell patch clamp technique, the effects of PAF on APD₉₀, I_K1 and I_K were investigated in enzymatically dispersed single guinea-pig ventricular myocytes. RESULTS: With 5 mmol/L ATP in the pipette electrode, 1 μmol/L PAF increased APD₉₀ from (225.8±23.3) ms to (352.8±29.8) ms (n=5, P<0.05), decreased I_K1 and I_K tail currents from (-6.1±1.3) nA to (-5.6±1.1) nA (n=5, P<0.05) at -120 mV and from (173.5±16.7) pA to (152.1±11.5) pA (P<0.05, n=4) at +30 mV, respectively. In contract, without ATP in the pipette electrode, 1 μmol/L PAF shortened APD₉₀ from (153.0±24.6) ms to (88.2±19.4) ms (n=5, P<0.01). Incubation of myocytes with 1 μmol/L glibenclamide, a blocker of I_KATP restored prolongation of APD induced by PAF. CONCLUSION: In guinea-pig ventricular myocytes, with 5 mmol/L ATP in the pipette, PAF prolonged APD partly due to the inhibition of I_K and I_K1, while with 0 mmol/L ATP in the pipette, PAF induced an activation of I_KATP, hence a decrease in APD was observed. Therefore, PAF might amplify the heterogeneity between ischemia and normal cardiac myocytes during ischemic reperfusion, which might play a vital role in the pathogenesis of the arrhythmias induced by ischemia/reperfusion.     

Effects of cardiomyopeptidin on sodium current in ventricular myocytes of guinea pigs

AIM: To determine the effect of cardiomyopeptidin on sodium current (I_Na) in ventricular myocytes of guinea pigs and to explore the mechanism of cardiomyopeptidin action at the ionic channel level. METHODS: Single ventricular myocytes of guinea pigs were obtained by enzymatic dissociation method. The whole-cell patch-clamp recording technique was used to record the change of I_Na. RESULTS: Cardiomyopeptidin (1, 5, 10, 50, 100 and 500 mg/L) decreased I_Na in a dose-dependent manner. The inhibition rates were (0±1)%, (6±2)%, (10±2)%, (15±1)%, (22±9)% and (30±6)%, respectively. The time to peak (TTP) was delayed from (2.8±0.7) ms to (3.0±0.8) ms (P<0.05) by cardiomyopeptidin (50 mg/L). In the presence of cardiomyopeptidin (50 mg/L), the current density-voltage curve of I_Na was shifted and without change of its active potential, peak potential, reversal potential, and the shape of the curve. The steady activation curve, the steady inactivation curve and the steady inactivation recovery curve of I_Na were not affected. CONCLUSION: Cardiomyopeptidin inhibits the I_Na in guinea pig ventricular myocytes, which may be one of the mechanisms of its antiarrhythmic effect.     

Effects of simvastatin on transient outward potassium current in ventricular myocytes of normocholesterolemic rabbits suffering from ischemia and reperfusion

AIM: To investigate the effects of simvastatin on transient outward potassium current (Ito) in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the cellular (ionic) mechanism of statin treatment for antiarrhythmia. METHODS: Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (statin) and sham-operation control group (sham). Anesthetized rabbits were subjected to 30 min ischemia by ligation of the left anterior descending coronary artery and 60 min reperfusion after oral administration of simvastatin at dose of 5 mg·kg-1·d-1(statin group) or placebo (I-R group) for 3 d. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I-R, statin group and the same anatomy region in sham. Whole cell patch clamp technique was used to record Ito. Simultaneously, the level of serum cholesterol was examined. RESULTS: No significant difference in serum cholesterol concentration among three groups was observed. The Ito current density (at +60 mV) was significantly decreased in I-R ［(9.49 ±1.91) pA/pF, n=11］ compared with sham ［(17.41± 3.13) pA/pF, n=15, P＜0.01］ and statin ［(15.24 ± 2.41) pA/pF, n=11, P＜0.01］, although there was slight reduction in statin group compared with sham (P＜0.05). CONCLUSION: Ischemia-reperfusion induces significant down-regulation of Ito, which may underlie the altered electrical activity and prolong abnormal transmembrane action potential duration of the surviving ventricular myocytes. Pretreatment with simvastatin attenuates these changes without lowering the serum cholesterol level, suggesting that simvastatin may reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.     

Effects of piperine on abnormalities of inward rectifier potassium current and ultra rapid delayed rectifier potassium current induced by hydrogen peroxide in rabbit atrial myocytes

AIM: To study the protective effect of piperine on abnormalityies of inward rectifier potassium current (I_K1) and ultra rapid delayed rectifier potassium current (I_KUr) induced by hydrogen peroxide (H₂O₂) in single rabbit atrial myocytes. METHODS: The technique of whole-cell patch-clamp was used to study the effect of H₂O₂ at concentration of 50 μmol/L on I_K1 and I_KUr in single rabbit atrial myocytes. The protective effect of pretreatment with piperine (7 μmol/L) was also observed. RESULTS: The piperine at concentration of 7 μmol/L had no significant effect on I_K1 and I_KUr and their channel dynamics. In the presence of H₂O₂ at concentration of 50 μmol/L, the peak currents of I_K1 and I_KUr reduced significantly (P<0.05).The steady-state activation curve of I_KUr was shifted right, the steady-state inactivation curve of I_KUr was shifted left, and the recovery from inactivation of I_KUr was shifted downward. The I_KUr showed frequency-dependent characteristics. Piperine at concentration of 7 μmol/L significantly alleviated the inhibitory effect of H₂O₂ on I_K1 and I_KUr (P<0.01). In addition, piperine protected against the changes of I_KUr dynamics induced by H₂O₂. CONCLUSION: Piperine alleviates the abnormalities of I_K1 and I_KUr induced by oxidative stress in atrial myocytes.     

Effects of ischemic preconditioning on hepatocyte apoptosis induced by hepatic ischemia-reperfusion in cirrhotic rats

AIM:To investigate the protective effect of ischemic preconditioning (IPC) on hepatic ischemia-reperfusion(I/R) injury in cirrhotic rats and its possible mechanism. METHODS:Hepatic I/R was induced by Pringle maneuver. The cirrhotic rats were randomized into three groups: Group A: before 30 min of ischemia, a short period of 5 min ischemia and 5 min reperfusion were given; Group B: before 30 min of ischemia, a short period of 10 min ischemia and 10 min of reperfusion were given; Group C: 30 min ischemia only. The serum alanine transferase (ALT), hepatic Fas-mRNA, caspase-3 activity and hepatocyte apoptosis were analyzed. RESULTS:The 7-day survival rate in the group A and B were 100%, respectively. However, it was only 62.5% in the group C. After 6 h of reperfusion, the ALT levels in both group A and B were significantly lower than that of in group C, P＜0.01. The ALT level of group A was also lower than that of group B, P＜0.01. The hepatic Fas-mRNA expression, caspase-3 activity and apoptotic hepatocyte in group A were significantly lower than those of in group C, P＜0.01. CONCLUSIONS:IPC has significant protective effect against hepatic I/R injury. An IPC with 5 min of ischemia and 5 min of reperfusion has the maximal protective effect. The protective mechanism of IPC against hepatic I/R injury is via down-regulation of Fas-mRNA expression, inhibiting caspase-3 activity and subsequently inhibiting hepatocyte apoptosis.     

Effects of hydrogen peroxide on sodium current in acutely isolated rat hippocampal CA1 neurons

AIM and METHODS: The effects of hydrogen peroxide on Na⁺ currents were studied in freshly dissociated rat hippocampal CA1 neurons using the whole-cell patch-clamp techinique. RESULTS: ①H₂O₂ caused a dose-dependent and voltage-dependent increase in the voltage-activated Na⁺ currents. The amplitudes of Na⁺ currents were increased (48.0±4.2)% and (88. 2±5. 1)% (n=10) by H₂O₂ at 10 μmol/L and 100 μmol/L, respectively. ②H₂O₂ (10 μmol/L) did not affect the activation process, but changed the inactivation process significantly. Before and after application of 10 μmol/L of H₂O₂, the half-inactivation voltage was (-64.58±1.22)mV and (-53.55±0.94)mV (n=10, P<0.01), but the slope factor was not changed. CONCLUSION: As a product of oxidation metabolism, H₂O₂ is related to some diseases in the central nervous system.     

Volume-activated chloride channel exists in CD133+ lung cancer stem cells

AIM: To analyze the possibility that volume-activated chloride channel (VACC) exists in tumor stem cells. METHODS: CD133⁺ cells were purified by magnetic cell separation (MACS) system from non-small-cell lung cancer cell line A549. The purity of the cells was detected by flow cytometry. VACC current was recorded with whole-cell patch-clamp. RESULTS: The purity of CD133⁺ cells isolated from A549 by MACS was 92.14%. VACC current was recorded in the 22/40(55%) CD133⁺ cells of A549 by whole-cell patch-clamp. CONCLUSION: VACC exists in CD133⁺ lung cancer stem cells.     

Effect of pretreatment with 11,12-EET on myocardial ischemia/reperfusion injury in rats

AIM: To examine the effect of pretreatment with low-concentration of 11, 12-epoxyeicosatrienoic acid(EET) on myocardial ischemia/reperfusion injury in rats. METHODS: After tracheotomy, myocardial ischemia/reperfusion was produced by occlusion and release of the left anterior descending artery(LAD) of the rats. Ischemic preconditioning(IP) was made by two times of ischemia(5 min)/reperfusion(5 min). The experiment was conducted in three groups: control,IP and pretreatment with 11,12-EET(6.24×10^-8 mol/L), and each group was subdivided into two subgroups:A,the rats were subjected to ischemia(10 min)/reperfusion(10 min) and arrhythmias during the whole periods were monitored; The rats in B were subjected to ischemia(60 min)/reperfusion(30 min) and arrhythmias, cardiac funtion and myocardial infarction size were documented. RESULTS: Both IP and pretreatment with 11,12-EET could protect the heart against arrhythmias, cardiac disfunction and myocardial infarction. CONCLUSION: Pretreatment with 11,12-EET had protective effect on myocardium in case of ischemia/reperfusion, which was similar to ischemic preconditioning.     

Changes of large-conductance calcium-activated potassium channel in gastric smooth muscle cells of diabetic gastroparesis rats

AIM: To discuss the relevance between the pathogenesis of diabetic gastroparesis and the large-conductance calcium-activated potassium channels (BK_Ca) in gastric smooth muscle cells. METHODS: The SD rats were randomly divided into control group and model group. The gastric smooth muscle cells of the SD rats were enzymatically isolated in a low calcium solution containing papain. The current was recorded by patch clamp single channel recording technique. The expression of KCNMA and KCNMB1 were observed by the method of immunohistochemistry. RESULTS: The value of BK_Ca single channel conductance was (220.10±10.90) pS; the channels had distinct voltage dependent and calcium dependent characteristics. In outside-out patch (Vm =+30 mV), the activation of BK_Ca was blocked by 200 nmol/L IbTX completely. Compared with control group, the open probability and amplitude of current in model group significantly increased, while the mean open time and mean close time significantly decreased. Compared with control group, the expression of KCNMB1 in model group was significantly increased. CONCLUSION: Up-regulation of β1-subunit and increase in BK_Ca functional activities may be associated with diabetes gastroparesis in rats.     

Cardiac IKs as repolarization reserve plays a role in gender difference of diabetic QT prolongation

AIM: To explore the basic ionic mechanisms underlying long-QT syndrome by observing the changes of slowly activating outward rectifying potassium current (I_Ks) and its proteins in abnormal QT prolongation in different genders of diabetic rabbits.METHODS: A single injection of pre-warmed (37 ℃) alloxan (140 mg/kg) was used to establish a rabbit model of insulin-dependent diabetes mellitus. Eight weeks after alloxan injection, the levels of blood glucose in the rabbits were monitored and standard lead II electrocardiogram was recorded. The myocardial cells were isolated from the ventricle of the rabbits via enzymatic digestion. Whole-cell patch clamp technique was performed to study the action potential duration (APD) and I_Ks. The changes of both KvLQT1 and mink proteins were detected by Western blotting analysis.RESULTS: The QT interval and APD were prolonged apparently both in male and female diabetic rabbits. The increased APD/QT-I of the male diabetic rabbits is more remarkable than that of the female. The I_Ks step current density of the male diabetic rabbits was decreased at test potentials ranging from+40 mV to+70 mV compared with that of the control animals (P<0.05), which was lowered from (3.08±0.67) pA/pF (n=17) to (1.27±0.20) pA/pF (n=16) at+70 mV. However, the I_Ks step current density of the female diabetic rabbits was increased at test potentials ranging from 0 mV to+70 mV compared with that of control group (P<0.05), which was increased from (1.56±0.20) pA/pF (n=13) to (3.65±0.50) pA/PF (n=14) at+70 mV. The expression of KvLQT1 and mink in male diabetic group decreased by 21.6% and 18.5%, respectively. However, the expression of KvLQT1 and mink in female diabetic group were increased by 42.3% and 20.5%, respectively.CONCLUSION: The I_Ks may be a protective factor in the early period of diabetic development in female rabbits. As a repolarization reserve, cardiac I_Ks is likely to restrict the effects of excessively slowing repolarization.     

Effect of garlicin on sodium channel current in rat ventricular myocytes

AIM: To observe the effect of garlicin on sodium channel(I_Na) in isolated ventricular myocytes of rats. METHODS: The ventricular myocytes of rats were obtained by enzymatic dissociation and treated with different concentrations of garlicin. The change of I_Na was recorded by the technique of whole-cell patch clamp recording.RESULTS: Garlicin decreased the I_Na of isolated ventricular myocytes in a dose- and voltage-dependent manner. The current density was elevated to peak under the condition that the membrane voltage was -40 mV before treated with garlicin. The current density was decreased by 48% from peak after treated with 500 μmol/L garlicin . No significant change of the active curve with the use of garlicin was observed. The median inactive voltages of the inactive curves before and after garlicin treatment were (-88.61±9.60) mV and (-103.03±8.90) mV (P<0.01), respectively, and the slopes were -7.85±0.88 and -7.55±2.75 (P>0.05), respectively, indicating that garlicin made a shift to the negative direction. CONCLUSION: Garlicin treatment induced the current density-voltage curve of I_Na to shift up and significantly decreased the current density. The inactive curve of sodium channel moved to the left, while the current density was not decreased after treated with garlicin. Garlicin blocks sodium channel in its inactive state in a dose- and voltage-dependent manner.     

Effects of ischemic preconditioning on cardiac myocyte apoptosis and expression of bcl-2 during myocardial ischemia/reperfusion in rats

AIM:To explore the effect of ischemic preconditioning on cardiac myocyte apoptosis and the expression of bcl-2 during myocardial ischemia/reperfusion in rats. METHODS:We use TUNEL,immunohistochemical and in situ hybridization(ISH) methods to detect the cardiac myocyte apoptosis and the expression of bcl-2 during myocardial ischemia/reperfusion in rats. RESULTS:①The numbers of positive cardiac myocyte nuclear and the percentage of positive cardiac myocyte nuclear in IP+I/R_3h group decreased significantly(P<0.05,P<0.01)compared with I/R_3h group,respectively.②The numbers of bcl-2 protein positive cardiomyocyte and the percentage of bcl-2 protein positive cardiomyocyte in IP+I/R_3h group were higher(P<0.01)than that of I/R_3h group,respectively.The numbers of positive bcl-2 mRNA cardiomyocyte and the percentage of positive bcl-2 mRNA cardiomyocyte in IP+I/R_1h group were higher(P<0.01)than that of I/R_1h group,respectively.CONCLUSION:① The first window of IP's protection could reduce cardiomyocyte apoptosis significantly.② Up-regulating the protein expression of bcl-2 in cardiomyocytes during I/R may be one of the mechanisms of first window of IP's protection.     

Effect of fluvastatin on left ventricular remodeling after myocardial infarction in rats

AIM: To clarify the protective effect of long-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on ventricular remodeling after myocardial infarction (MI) in rats and its mechanisms. METHODS: Myocardial infarction were established by ligated left coronary anterior artery in SD rats, 24 hours after the operation, the survival rats were treated by gavage fluvastatin (20 mg·kg^-1·d^-1) or distilled water for 8 weeks. Doppler echocardiography, homodynamic and cardiac histomorphometry were used to assess the ventricular remodeling and cardiac function. The plasma levels of total cholesterol (Tch), creatinine (Cr), glutamic-oxal (o) acetic transaminase (AST), lipid peroxidation (LPO), glutathione perioxidase (GSH-PX), nitrogen monoxide (NO₂^-/NO₃^-) were detected. RESULTS: The Tch, Cr and AST were not significant difference in groups. Left ventricular end-diastole pressure, right relative weight, left ventricular posterior wall thickness, collagen volume fraction and the lung weight were decreased in AMI+fluvastatin group compared to AMI group (P＜0.05, P<0.01); The levels of LPO, NO₂^-+NO₃^- in plasma and LPO in myocardium decreased, but plasma GSH-PX level increased in AMI+fluvastatin group (P＜0.05). CONCLUSION: Fluvastatin ameliorates the ventricular structural remodeling in a rat model of infarction, and delays the development of heart failure. The anti-oxidation mechanism of fluvastatin may take part in this process.