Ionic mechanism of shock-induced arrhythmias: role of intracellular calcium.

Abstract

Strong electrical shocks can cause focal arrhythmias, the mechanism of which is not well known. Strong shocks have been shown to produce diastolic Ca(i)(2+) increase, which may initiate focal arrhythmias via spontaneous Ca(i)(2+) rise (SCR), activation of inward Na(+)/Ca(2+) exchange current (I(NCX)), and rise in membrane potential (V(m)). It can be hypothesized that this mechanism is responsible for generation of shock-induced arrhythmias. The purpose of this study was to examine the roles of SCRs and I(NCX) in shock-induced arrhythmias. The occurrence of SCRs during shock-induced arrhythmias was assessed in neonatal rat myocyte cultures. Simultaneous V(m)-Ca(i)(2+) optical mapping at arrhythmia source demonstrated that V(m) upstrokes always preceded Ca(i)(2+) transients, and V(m)-Ca(i)(2+) delays were not different between arrhythmic and paced beats (5.5 ± 0.9 and 5.7 ± 0.4 ms, respectively, P = .5). Shocks caused gradual rise of diastolic Ca(i)(2+) consistent with membrane electroporation but no significant Ca(i)(2+) rises immediately before V(m) upstrokes. Application of the Ca(i)(2+) chelator BAPTA-AM (10 μmol/L) decreased the duration of shock-induced arrhythmias whereas application of the I(NCX) inhibitor KB-R7943 (2 μmol/L) increased it, indicating that, despite the absence of SCRs, changes in Ca(i)(2+) affected arrhythmias. It is hypothesized that this effect is mediated by Ca(i)(2+) inhibition of outward I(K1) current and destabilization of resting V(m). The possible role of I(K1) was supported by application of the I(K1) inhibitor BaCl(2) (0.2 mmol/L), which increased the arrhythmia duration. Shock-induced arrhythmias in neonatal rat myocyte monolayers are not caused by SCRs and inward I(NCX). However, these arrhythmias depend on Ca(i)(2+) changes, possibly via Ca(i)(2+)-dependent modulation of outward I(K1) current.