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(Circulation Research. 2000;87:453.)
© 2000 American Heart Association, Inc.

Integrative Physiology

Nonlinear Changes of Transmembrane Potential During Defibrillation Shocks

Role of Ca²⁺ Current

Eric R. Cheek, Raymond E. Ideker, Vladimir G. Fast

From the Departments of Biomedical Engineering (E.R.C., R.E.I., V.G.F.), Medicine (R.E.I.), and Physiology (R.E.I.), University of Alabama at Birmingham, Birmingham, Ala.

Correspondence to Vladimir G. Fast, PhD, University of Alabama at Birmingham, 1670 University Blvd, VH B149, Birmingham, AL 35294. E-mail fast{at}crml.uab.edu

Abstract—Defibrillation shocks induce complex nonlinear changes of transmembrane potential (V_m). To elucidate the ionic mechanisms of nonlinear V_m, we studied the effects of ionic channel blockers on V_m in geometrically defined myocyte cultures. Experiments were carried out in cell strands with widths of 0.2 mm (narrow strands) and 0.8 mm (wide strands) produced using a technique of directed cell growth. Uniform-field shocks were applied across strands during the action potential (AP) plateau, and the distribution of shock-induced V_m was measured using an optical mapping technique. Nifedipine and 4-aminopyridine were applied to inhibit the L-type calcium current (I_Ca) and the transient outward current (I_to), respectively. In control conditions, the distribution of V_m across cell strands was highly asymmetrical with a large ratio of negative to positive V_m (V^-_m/V⁺_m) measured at the opposite strand borders. Application of nifedipine caused a large increase of V⁺_m and a decrease of V^-_m/V⁺_m, indicating involvement of I_Ca in the asymmetrical V_m, likely as a result of the outward flow of I_Ca when V_m exceeded the I_Ca reversal potential. V^-_m decreased in the narrow strands but remained unchanged in the wide strands, indicating that the changes of V^-_m were caused by electrotonic interaction with an area of depolarization. 4-Aminopyridine did not change V^-_m/V⁺_m. These results provide evidence that (1) the asymmetry of shock-induced V_m during the AP plateau is due to outward flow of I_Ca in the depolarized portions of the strands, (2) I_to is not involved in the mechanism of V_m asymmetry, and (3) the effects of drugs on V_m are modulated by the tissue geometry.

Key Words: electrophysiology • defibrillation • mapping • voltage-sensitive dyes

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