The Electrophysiologic Study Of Taurine Magnesium Coordination Compound On Abnormal Ion Channel Induced By Hypoxia/Reoxygenation In Cardiomyocytes Of Rat

Aim:Taurine magnesium coordination compound (TMCC) is a new effective compound synthesized by our laboratory and has antiarrhythmic effects.But the mechanisms of its antiarrhythmic action remains to be clarified. In this study we investigate the effects of TMCC on abnormal sodium current (INa), L-type calcium current (Ica,L) in rat ventricular cardiomyocytes suffered from hypoxia/reoxygenation to find out the mechanism of antiarrhythmic effect.Methods:Enzymatic dissociation was used to get single rat ventricular myocytes and whole-cell patch clamp was used to record INa, ICa,L in ventricular cardiomyocytes suffered from hypoxia/reoxygenation in rat under amiodarone and different concentrations of TMCC.Results:1. In hypoxia/reoxygenation model, peak INa decreased from (56.89±2.07) pA/pF to (35.05±1.52) pA/pF(n=6, P<0.01), which was restored to (35.78±1.95) pA/pF(n=6, P>0.05), (41.52±0.86) pA/pF, (48.34±0.99) pA/pF(n=6, P<0.01) by TMCC(100,200, 400μmol·L-1).24.24μmol·L-1 amidodarone restored peak INa to (39.44±1.24) pA/pF (n=6, P<0.01). The INa I-V curves upward shift induced by hypoxia/reoxygenation were inhibited by TMCC and amiodarone.2.Compared to control group, hypoxia/reoxygenation group turned INa steady-state activation curves to right and inactivation curves to left, which made activate slowly and inactivate quickly, TMCC (200,400μmol·L-1) and amiodarone can restore the left shift inactivation curves, but they have no effects to the activation curves; In hypoxia/reoxygenation model, sodium channel t-value was increased, decay time was prolonged at the testing potential of-60 mV, TMCC (400μmol·L-1) and amiodarone can restore the increase of t-value and shorten the delay time.3.In hypoxia/reoxygenation model, peak ICa,L increased from(3.35±0.50) pA/pF to (5.69±0.25) pA/pF(n=6, P<0.0l),which was restored to (5.28±0.18) pA/pF(n=6, P>0.05), (4.41±0.22) pA/pF, (3.82±0.21) pA/pF(n=6, P<0.01) by TMCC (100,200, 400μmol·L-1).24.24μmol·L-1 amidodarone restored peak ICa,L to (3.66±0.27) pA/pF (n=6, P<0.01). The ICa,L I-V curves downward shift induced by hypoxia/ reoxygenation were inhibited by TMCC and amiodarone.4. Compared to control group, hypoxia/reoxygenation turned ICa,L steady-state activation curves to left and inactivation curves to right, which made activate quickly and inactivate slowly, TMCC (200,400μmol·L-1) and amiodarone can restore the left shift activation curves and right shift inactivation curves. About t-value, at the testing potential of+10 mV, there were no differents among control, hypoxia/reoxygenation, amidodarone and various concentrations TMCC group.Conclusion:1. TMCC(200,400μmol·L-1)can concentration-dependently restore the decrease of peak INa and up-shift of I-V curves due to hypoxia/reoxygenation by inhibiting inactivate process, but they have no effects to the activation curves.2. TMCC can concentration-dependently restore the increase of calcium current and down-shift of I-V curves due to hypoxia/reoxygenation by inhibiting activate process and promoting inactivate process.