Copyright © 2006, European Society of Cardiology
Shock-induced changes of Cai2+ and Vm in myocyte cultures and computer model: Dependence on the timing of shock application
Department of Biomedical Engineering, University of Alabama at Birmingham, 1670 University Blvd, VH B126, Birmingham, Alabama 35294, United States
* Corresponding author. Tel.: +1 205 975 2119; fax: +1 205 975 4720. Email address: fast{at}crml.uab.edu
Objectives: Responses of Cai2+ 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 
V+m and V–m. Simulations indicated that the Cai2+ decrease at V+m sites was caused by reversed outward flow of L-type Ca2+ current (ICaL), while the Cai2+ decrease at V–m sites was due to the NaCa exchanger (NCX). At intermediate delays (40–150 ms), shocks caused a Cai2+ decrease at sites of V–m and an increase at sites of V+m. Simulations indicated that the Cai2+ increase at V+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 V+m and no change at V–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 V+m. Shock-induced Cai2+ changes in different AP phases are primarily determined by combination of ICaL and NCX.
KEYWORDS Calcium; Computer modeling; Defibrillation; Mapping; Membrane potential
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