Effects of mibefradil, a T-type calcium current antagonist, on electrophysiology of Purkinje fibers that survived in the infarcted canine heart

Mibefradil's Effects on Canine Purkinje Myocytes. Introduction: We studied the effects of mibefradil (MIB), a nondihydropyridine T-type Ca2+ channel a ntagonist, on T- and L-type Ca2+ (I-CaT, I-CaL) currents in Purkinje myocyt es dispersed from the subendocardium of the left ventricle of normal (NZPC) and 48-hour infarcted (IZPC) hearts. Methods and Results: Currents were recorded with Cs+- and EGTA-rich pipette s and in Na+-K+-free external solutions to eliminate overlapping currents. In all cells, I-Ca was reduced by MIB (0.1 to 10 mu M). No change in the ti me course of decay of peak I-Ca was noted. Average peak T/L ratio decreased in NZPCs but not IZPCs with 1 mu M MIB. Steady-state availability of I-CaL was altered with 1 mu M MIB in both cell types (mean +/- SEM) (V-0.5 = -22 +/- 4 mV for NZPC and -25 +/- 5 mV for IZPC before drug; -63 +/- 9 mV for NZPC and -67 +/- 6 mV for IZPC after drug; P < 0.05). For I-CaT, V-0.5 (-50 +/- 3 mV for NZPC and -52 +/- 1 mV for IZPC before drug) shifted to -60 +/ - 2 mV (NZPC) and -62 +/- 3 mV (IZPC) (P < 0.05) after drug. We also determ ined the effects of MIB on spontaneously beating Purkinje normal fibers and on depolarized abnormally automatic fibers from the infarcted heart using standard microelectrode techniques. When NZPC and IZPC fibers were superfus ed with [K+](o) = 2.7 mM, MIB 3 mu M and 10 mu M had no effect on rate or t he maximum diastolic potential, but action potential plateau shifted to mor e negative values, the slope of repolarization phase 3 decreased, and actio n potential duration increased. Conclusion: MIB blocks L- and T-type Ca2+ currents in Purkinje myocytes but lacks an effect on either normal or abnormal automaticity in Purkinje fibe rs.