Ionic mechanism of shock-induced arrhythmias: Role of intracellular calcium

BackgroundStrong electrical shocks can cause focal arrhythmias, the mechanism of which is not well known. Strong shocks have been shown to produce diastolic Cai2+ increase, which may initiate focal arrhythmias via spontaneous Cai2+ rise (SCR), activation of inward Na+/Ca2+ exchange current (INCX), and rise in membrane potential (Vm). It can be hypothesized that this mechanism is responsible for generation of shock-induced arrhythmias.ObjectiveThe purpose of this study was to examine the roles of SCRs and INCX in shock-induced arrhythmias.MethodsThe occurrence of SCRs during shock-induced arrhythmias was assessed in neonatal rat myocyte cultures.ResultsSimultaneous Vm-Cai2+ optical mapping at arrhythmia source demonstrated that Vm upstrokes always preceded Cai2+ transients, and Vm-Cai2+ 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 Cai2+ consistent with membrane electroporation but no significant Cai2+ rises immediately before Vm upstrokes. Application of the Cai2+ chelator BAPTA-AM (10 μmol/L) decreased the duration of shock-induced arrhythmias whereas application of the INCX inhibitor KB-R7943 (2 μmol/L) increased it, indicating that, despite the absence of SCRs, changes in Cai2+ affected arrhythmias. It is hypothesized that this effect is mediated by Cai2+ inhibition of outward IK1 current and destabilization of resting Vm. The possible role of IK1 was supported by application of the IK1 inhibitor BaCl2 (0.2 mmol/L), which increased the arrhythmia duration.ConclusionShock-induced arrhythmias in neonatal rat myocyte monolayers are not caused by SCRs and inward INCX. However, these arrhythmias depend on Cai2+ changes, possibly via Cai2+-dependent modulation of outward IK1 current.