Shock-induced changes of Cai2+ and Vm in myocyte cultures and computer model: Dependence on the timing of shock application

Academic Article

Abstract

  • Objectives: Responses of Cai 2+ to electrical shocks are believed to be important in defibrillation but measurements of shock-induced Cai2+ changes during different phases of the action potential (AP) are lacking. The effects of shocks on Cai2+ and Vm were investigated in geometrically defined cell cultures and in a computer model. Methods: Uniform-field shocks (E = 10.4 ± 0.9 V/cm) were applied 15-300 ms after AP upstroke in strands of cultured neonatal rat myocytes. Optical mapping was used to measure shock-induced Cai2+ and Vm changes. A rat ionic model was used to elucidate ionic mechanisms of Cai2+ responses. Results: In experiments and simulations, shocks applied with short delays (15-40 ms) caused a transient decrease of Cai2+ at sites of both ΔV+m and ΔV-m. Simulations indicated that the Cai2+ decrease at ΔV+m sites was caused by reversed outward flow of L-type Ca2+ current (ICaL), while the Cai2+ decrease at ΔV-m sites was due to the NaCa exchanger (NCX). At intermediate delays (40-150 ms), shocks caused a Cai2+ decrease at sites of ΔV-m and an increase at sites of ΔV+m. Simulations indicated that the Cai2+ increase at ΔV+m sites was caused by transient reactivation of ICaL combined with a reverse-mode operation of NCX. Shocks applied at long delays (150-300 ms) caused a Cai2+ increase at ΔV+m and no change at ΔV-m sites. Conclusion: Effects of shocks on Cai2+ depend on the timing of shock application. Shocks applied during the early AP cause a transient Cai2+ decrease, while later in AP shocks induce a Cai2+ increase at sites of ΔV+m. Shock-induced Cai2+ changes in different AP phases are primarily determined by combination of ICaL and NCX. © 2006 European Society of Cardiology.
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    Author List

  • Raman V; Pollard AE; Fast VG
  • Start Page

  • 101
  • End Page

  • 110
  • Volume

  • 73
  • Issue

  • 1