Effects of Mibefradil, a T-Type Calcium Current Antagonist, on Electrophysiology of Purkinje Fibers that Survived in the Infarcted Canine Heart

• Published in: Journal of cardiovascular electrophysiology Vol. 10; no. 9; pp. 1224 - 1235
• Main Authors: PINTO, JUDITH M.B., SOSUNOV, EUGENE A., GAINULLIN, RAVIL Z., ROSEN, MICHAEL R., BOYDEN, PENELOPE A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-1999
• Subjects: Action Potentials; Animals; automaticity; Calcium - physiology; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Dogs; Electrophysiology; L-type Ca2+ current; Male; mibefradil; Mibefradil - pharmacology; Mibefradil - therapeutic use; Myocardial Contraction - drug effects; myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Purkinje Fibers - physiopathology; Purkinje myocytes; Ro 40-5967; T-type Ca2+ current arrhythmias
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/j.1540-8167.1999.tb00300.x

Mibefradil's Effects on Canine Purkinje Myocytes. Introduction: We studied the effects of mibefradil (MIB), a nondihydropyridine T‐type Ca2+ channel antagonist, on T‐ and L‐type Ca2+ (ICaT, ICaL) currents in Purkinje myocytes 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 pipettes and in Na+ ‐K+ ‐free external solutions to eliminate overlapping currents. In all cells, ICa was reduced by MIB (0.1 to 10 μM). No change in the time course of decay of peak ICa was noted. Average peak T/L ratio decreased in NZPCs hut not IZPCs with 1 μM MIB. Steady‐state availability of ICaL was altered with I μM MIB in both cell types (mean ± SEM) (V0.5= ‐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 ICaT V0.5 (‐50 ± 3 mV for NZPC and ‐52 ± 1 mV for IZPC before drug) shifted 10 ‐60 ± 2 mV (NZPC) and ‐62 ± 3 mV (IZPC) (P < 0.05) after drug. We also determined the effects of MIB on spontaneously heating Purkinje normal fibers and on depolarized abnormally automatic fibers from the infarcted heart using standard microelectrode techniques. When NZPC and IZPC fibers were superfused with [K+]0= 2.7 mM, MIB 3 μM and 10 μM had no effect on rate or the maximum diastolic potential, but action potential plateau shifted to more negative values, the slope of repolarization phase 3 decreased, and action potential duration increased.
Conclusion: MIB blocks L‐ and T‐type Ca2+ currents in Purkinje myocytes hut lacks an effect on either normal or abnormal automaticity in Purkinje fibers.