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Effects of Mibefradil, a T‐Type Calcium Current Antagonist, on Electrophysiology of Purkinje Fibers that Survived in the Infarcted Canine Heart
Author(s) -
PINTO JUDITH M.B.,
SOSUNOV EUGENE A.,
GAINULLIN RAVIL Z.,
ROSEN MICHAEL R.,
BOYDEN PENELOPE A.
Publication year - 1999
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1999.tb00300.x
Subject(s) - mibefradil , purkinje fibers , electrophysiology , ventricle , medicine , endocardium , pacemaker potential , calcium , voltage dependent calcium channel , cardiology , biophysics , biology
Mibefradil's Effects on Canine Purkinje Myocytes. Introduction : We studied the effects of mibefradil (MIB), a nondihydropyridine T‐type Ca 2+ channel antagonist, on T‐ and L‐type Ca 2+ (I CaT , I CaL ) 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, I Ca was reduced by MIB (0.1 to 10 μM). No change in the time course of decay of peak I Ca was noted. Average peak T/L ratio decreased in NZPCs hut not IZPCs with 1 μM MIB. Steady‐state availability of I CaL was altered with I μM 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 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 Ca 2+ currents in Purkinje myocytes hut lacks an effect on either normal or abnormal automaticity in Purkinje fibers.