Effect of carvedilol on T-type calcium current in myocytes of non-infarcted area of the rabbit healed myocardial infarction

This article reports the investigation of the effect of carvedilol (Car) on T-type calcium current (I_Ca,T) of noninfarcted ventricular myocytes in rabbit models of healed myocardial infarction (HMI).  Rabbits with left anterior descending artery ligation were prepared and allowed to recover for 8 weeks, as HMI group.  animals undergoing an identical surgical procedure without coronary ligation were served as the sham-operated group (sham group).  Whole cell voltage-clamp techniques were used to measure and compare currents in cells from the different groups.  Noting that I_Ca,T density in HMI cells increased markedly to −2.36 ± 0.12 pA/pF (at −30 mv) compared with cells of sham, where little I_Ca,T (−0.35 ± 0.02 pA/pF) was observed.  Meanwhile, further analysis revealed a significant hyperpolarizing shift of steady-state activation curve of I_Ca,T in HMI cells, where the time constants of deactivation were prolonged and the time of recovery from inactivation was shortened.  Finally, the amplitude of I_Ca,T was increased.  Carvedilol (1 µmol·L⁻¹) was found to decrease the amplitude of I_Ca,T to −1.38 ± 0.07 pA/pF through inhibiting process of I_Ca,T activation.  Furthermore, carvedilol delayed recovery from inactivation of I_Ca,T and shortened the time constants of deactivation in HMI cells.  This study suggested that the application of carvedilol in HMI cells contributes to the dynamic changes in I_Ca,T and may account for reduction of incidence of arrhythmia after myocardial infarction.