Shock-induced changes of Ca(i)2+ and Vm in myocyte cultures and computer model: Dependence on the timing of shock application.
OBJECTIVE
Responses of Ca(i)2+ to electrical shocks are believed to be important in defibrillation but measurements of shock-induced Ca(i)2+ changes during different phases of the action potential (AP) are lacking. The effects of shocks on Ca(i)2+ 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 Ca(i)2+ and Vm changes. A rat ionic model was used to elucidate ionic mechanisms of Ca(i)2+ responses.


RESULTS
In experiments and simulations, shocks applied with short delays (15-40 ms) caused a transient decrease of Ca(i)2+ at sites of both DeltaV(+)m and DeltaV(-)m. Simulations indicated that the Ca(i)2+ decrease at DeltaV(+)m sites was caused by reversed outward flow of L-type Ca2+ current (I(CaL)), while the Ca(i)2+ decrease at DeltaV(-)m sites was due to the NaCa exchanger (NCX). At intermediate delays (40-150 ms), shocks caused a Ca(i)2+ decrease at sites of DeltaV(-)m and an increase at sites of DeltaV(+)m. Simulations indicated that the Ca(i)2+ increase at DeltaV(+)m sites was caused by transient reactivation of I(CaL) combined with a reverse-mode operation of NCX. Shocks applied at long delays (150-300 ms) caused a Ca(i)2+ increase at DeltaV(+)m and no change at DeltaV(-)m sites.


CONCLUSIONS
Effects of shocks on Ca(i)2+ depend on the timing of shock application. Shocks applied during the early AP cause a transient Ca(i)2+ decrease, while later in AP shocks induce a Ca(i)2+ increase at sites of DeltaV(+)m. Shock-induced Ca(i)2+ changes in different AP phases are primarily determined by combination of I(CaL) and NCX.
Raman
Vidya
V
Department of Biomedical Engineering, University of Alabama at Birmingham, 1670 University Blvd, VH B126, Birmingham, Alabama 35294, USA.
Pollard
Andrew E
AE
Fast
Vladimir G
VG
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000628:therapy*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D003198:Computer Simulation; D004554:Electric Countershock; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger