Temperature and voltage dependence of sodium channel blocking and unblocking by O-demethyl encainide in isolated guinea pig myocytes

Journal of Cardiovascular Pharmacology
J A JohnsL M Hondeghem

Abstract

O-demethyl encainide (ODE) is a metabolite of encainide with potent antiarrhythmic effects. We studied block of sodium channels by ODE in isolated guinea pig ventricular myocytes, using both direct measurement of whole cell sodium current and Vmax. Specifically, we examined whether block by ODE was use-dependent, whether ODE blocked activated or inactivated channels, and whether ODE's effect depended on membrane potential. At cold temperatures (15-20 degrees C), ODE was a potent blocker of activated cardiac sodium channels, with little or no effect on inactivated channels. At these temperatures, there was no detectable diastolic recovery from block. Repeated depolarizations produced use-dependent unblocking, which increased as the holding potential was made more negative. At warmer temperatures, use-dependent unblocking was increased, the availability curve of sodium channels for use-dependent unblocking was less shifted toward negative potentials, and diastolic recovery from block became detectable, albeit slow (tau approximately 25 s). Our findings demonstrate that electrophysiologic effects of agents such as ODE may be both quantitatively and qualitatively different at cold temperatures than at normal body temperature. One s...Continue Reading

Citations

Aug 1, 1995·Pflügers Archiv : European journal of physiology·H WindischD Platzer
Oct 24, 1998·Progress in Biophysics and Molecular Biology·E Carmeliet, K Mubagwa
Nov 1, 2011·Journal of Cardiovascular Electrophysiology·Yoshino MinouraCharles Antzelevitch
Apr 15, 2011·British Journal of Pharmacology·Gary A GintantMichael K Pugsley
Jul 1, 1992·The American Journal of Emergency Medicine·A OrtsM M Puig
May 1, 1991·American Heart Journal·H BjørnstadH Refsum
May 8, 2013·Journal of Pharmacological and Toxicological Methods·Pierre MorissetteJoseph J Salata
Aug 5, 2008·American Journal of Physiology. Heart and Circulatory Physiology·K S DujardinL M Hondeghem

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