REDUCED CALCIUM CURRENTS IN SUBENDOCARDIAL PURKINJE MYOCYTES THAT SURVIVE IN THE 24-HOUR AND 48-HOUR INFARCTED HEART

Background The abnormal transmembrane action potentials of subendocardial Purkinje fibers that survive 24 to 48 hours after coronary artery occlusion can be a source of the multiform ventricular tachycardias that occur during this time. A change in the density or function of either or both the T-type and L-type cardiac Ca2+ channels may contribute to the altered electrical activity of these Purkinje myocytes. Methods and Results The purpose of this study was to determine the function of the T- and L-type Ca2+ currents (i(Cat) and i(CaL), respectively) in Purkinje myocytes dispersed from the subendocardium of the left ventricle 24 and 48 hours after coronary artery occlusion (IZPC(24) and IZPC(48), respectively). To do this we compared whole-cell Ca2+ currents from Purkinje myocytes enzymatically dispersed from free-running fiber bundles (SPCs), from the subendocardium of the noninfarcted canine heart (NZPCs), and from IZPC(24) and IZPC(48). I-CaL and i(Cat) were recorded with Cs+- and EGTA-rich pipettes and in Na+-K+-free external solutions to eliminate overlapping currents. I-CaL density was significantly reduced in IZPC(48), compared with NZPC or IZPC(24). This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of i(CaL). Replacement of Ca2+ with equimolar Ba2+ increased i(CaL) density in all cell types, but peak i(BaL) of IZPC(48) remained reduced compared with control i(BaL) values. T-type Ca2+ currents were recorded in all SPCs and NZPCs. In IZPC(24) and IZPC(48) there was a reduction in peak i(Cat) amplitudes and densities. This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of peak i(Cat). However, there was a hyperpolarizing shift in the steady-state availability relations in both IZPC(24) and IZPC(48). In addition, the maximally available i(Cat) in IZPC(24) was not different from control, whereas it was significantly reduced in IZPC(48). Conclusions The L-type I-Ca density in subendocardial Purkinje myocytes that survive in the infarcted heart is significantly decreased by 48 hours after the time of coronary artery occlusion. The peak T-type I-Ca density is decreased in subendocardial Purkinje myocytes that survive in the infarcted heart at 24 hours, but further reduction occurs in these myocytes by 48 hours. This loss in Ca2+ channel function could contribute to the abnormal transmembrane potentials of these myocytes surviving in the infarcted heart.