The Electrophysiologic Study Of Taurine Magnesium Coordination Compound Resist Arrhythmia Of Cardiac Muscle Cell Induced By Aconitine

Aim:Taurine-magnesium coordination compound (TMCC) is a new effective compound synthesised by our laboratory and has antiarrhythmic effects. But less information exists with regard to the mechanisms of its antiarrhythmic action. In this study we investigate the antiarrhythmic mechanism of TMCC on sodium current (INa), L-type calcium current (ICa,L) in rat ventricular cardiomyocytes of arrhythmia induced by aconitine.Methods:Enzymatic dissociation was used to get single rat ventricular myocytes and whole-cell patch clamp was used to record INa, ICa,L in normal and arrhythmic ventricular cardiomyocytes induced by aconitine in rat under amiodarone and different concentration of TMCC.Results:1. In normal ventricular cardiomyocytes of rat, TMCC (100,200,400μmol·L-1) decreased INa densities from (45.56±1.96)pA/pF to (42.42±4.75)pA/pF(n=5, P<0.05), (39.71±1.63)pA/pF(n=5, P<0.05), (37.59±4.75)pA/pF(n=5, P<0.01), respectively. The inhibition was in a concentration-dependent manner.24.24μmol·L-1 amiodarone decreased INa densities to (34.23±1.33)pA/pF (n=5, P<0.01). The INaⅠ-Ⅴcurve was shifted upwards by TMCC and amiodarone without changes of their active, peak and reverse potentials. TMCC (200,400μmol·L-1) and amiodarone turned INa steady-state activation and inactivation curves to right, which made activate and inactivate slowly.2. In arrhythmic ventricular cardiomyocytes induced by 1μmol·L-1 aconitine, INa densities increased from (45.56±1.96) pA/pF to (59.19±11.49) pA/pF, TMCC (100, 200,400μmol·L-1) could inhibit the action by aconitine and made theⅠ-Ⅴcurve upper shift in a concentration-dependent manner. The INa densities was decreased to (51.61±5.96)pA/pF, (41.50±5.50)pA/pF, (40.91±6.73)pA/pF(n=5,P<0.01), respectively.24.24μmol·L-1 amidodarone restored INa densities to (40.22±1.47)pA/pF (n=5, P<0.01).1μmol·L-1 aconitine turned INa steady-state activation and inactivation curves to left, which made activate and inactivate quickly, TMCC (100,200,400μmol·L-1) and amiodarone can make them normal.3. In normal ventricular cardiomyocytes of rat, TMCC (100,200,400μmol·L-1) changed ICa,L densities from (-4.31±1.62)pA/pF to (4.02±0.75)pA/pF (4.59±0.30)pA/pF, (5.17±0.20)pA/pF, respectively.400μmol·L-1 TMCC increased ICa,L densities significantly(n=5, P<0.01). Amiodarone decreased ICa,L densities to (2.84±0.19)pA/pF(n=5, P<0.01). The ICa,LⅠ-Ⅴcurve was shifted downwards by 400μmol·L-1TMCC, while upwards by amiodarone.TMCC turned the ICa,L steady-state activation curve to left, while turned inactivation curve to right. Amiodarone turned the ICa,L steady-state activation curve to right, while turned inactivation curve to left..4. In arrhythmic ventricular cardiomyocytes induced by 1μmol·L-1 aconitine, ICa,L densities increased from (-4.31±1.62) pA/pF to (6.40±1.92) pA/pF, TMCC (100, 200,400μmol·L-1) could inhibit the action by aconitine and made theⅠ-Ⅴcurve upper shift in a concentration-dependent manner. The ICa,L densities was restored to (6.14±1.84) pA/pF, (5.65±1.69) pA/pF, (5.18±1.56) pA/pF(n=5, P<0.05), respectively.24.24μmol·L-1 amidodarone restored ICa,L densities to (3.71±1.39) pA/pF (n=5, P<0.01).1μmol·L-1 aconitine turned ICa,L steady-state activation curve to left, while inactivation curve to right.400μmol·L-1TMCC turned activation curve to right and 24.24μmol·L-1amiodarone turned activation and inactivation curve to right.Conclusion:1. TMCC blocks INa in a concentration-dependent manner in normal ventricular cardiomyocytes, meanwhile, TMCC can restore INa to normal, which increased by aconitine. Amiodarone as control group had same action as TMCC.2. TMCC increases ICa,L in normal ventricular cardiomyocytes. Moreover,400μmol·L-1 TMCC can inhibit the action by aconitine and made ICa,L trend to be normal. All these may be the important antiarrhythmic mechanisms of TMCC.