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
Jan 19, 1993·European Journal of Pharmacology·A W Wamil, M J McLean
Oct 24, 1998·Progress in Biophysics and Molecular Biology·E Carmeliet, K Mubagwa
Jul 10, 2012·Open Biology·Claire A MartinChristopher L-H Huang
Feb 2, 2012·Epilepsia·Csilla EgriPeter C Ruben
Jul 14, 2010·Acta Physiologica·M BébarováJ Simurda
Apr 1, 1994·The Journal of Clinical Investigation·F N HauglandD L Packer
Jan 11, 2011·PloS One·Géza BereckiArie O Verkerk
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
Nov 10, 2016·PloS One·Ibrahim El-BattrawyXiao-Bo Zhou
Mar 1, 1990·Circulation Research·T Anno, L M Hondeghem
Feb 1, 1990·Circulation Research·D J Snyders, L M Hondeghem
Oct 15, 1996·Circulation·E Bou-Abboud, S Nattel
Aug 29, 1998·Circulation Research·J PuP A Boyden
Jul 1, 1997·Circulation Research·J Pu, P A Boyden
Jun 1, 1992·Circulation·C VillemaireS Nattel
Jan 21, 2006·Journal of Cardiovascular Pharmacology·Leif CarlssonStanley Nattel
Aug 5, 2008·American Journal of Physiology. Heart and Circulatory Physiology·K S DujardinL M Hondeghem
Aug 7, 2001·Journal of Cardiovascular Pharmacology·H M HimmelU Ravens
Feb 24, 1999·Journal of Cardiovascular Pharmacology·H M HimmelU Ravens
Aug 26, 1998·Cardiovascular Research·E Bou-Abboud, S Nattel