Nonlinear changes of transmembrane potential during defibrillation shocks: Role of Ca2+ current

Academic Article

Abstract

  • Defibrillation shocks induce complex nonlinear changes of transmembrane potential (ΔV(m)). To elucidate the ionic mechanisms of nonlinear ΔV(m), we studied the effects of ionic channel blockers on ΔV(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 ΔV(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 ΔV(m) across cell strands was highly asymmetrical with a large ratio of negative to positive ΔV(m) (ΔV-(m)/ΔV+(m)) measured at the opposite strand borders. Application of nifedipine caused a large increase of ΔV+(m) and a decrease of ΔV-(m)/ΔV+(m), indicating involvement of I(Ca) in the asymmetrical ΔV(m), likely as a result of the outward flow of I(Ca) when V(m) exceeded the I(Ca) reversal potential. ΔV-(m) decreased in the narrow strands but remained unchanged in the wide strands, indicating that the changes of ΔV-(m) were caused by electrotonic interaction with an area of depolarization. 4-Aminopyridine did not change ΔV-(m)/ΔV+(m). These results provide evidence that (1) the asymmetry of shock-induced ΔV(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 ΔV(m) asymmetry, and (3) the effects of drugs on ΔV(m) are modulated by the tissue geometry.
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    Author List

  • Cheek ER; Ideker RE; Fast VG
  • Start Page

  • 453
  • End Page

  • 459
  • Volume

  • 87
  • Issue

  • 6