
Sodium Channel Block by a Potent, New Antiarrhythmic Agent, Transcainide, in Guinea Pig Ventricular Myocytes
Author(s) -
Paul B. Bennett,
Roland X. Stroobandt,
Hugo Kesteloot,
Luc M. Hondeghem
Publication year - 1987
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-198706000-00004
Subject(s) - sodium channel , lidocaine , antiarrhythmic agent , electrophysiology , pharmacology , myocyte , sodium channel blocker , patch clamp , sodium , anti arrhythmia agents , chemistry , guinea pig , potency , medicine , biophysics , anesthesia , in vitro , biology , biochemistry , organic chemistry , heart disease , atrial fibrillation
Transcainide is a new lidocaine analog that has been shown to suppress a range of cardiac arrhythmias in an initial clinical trial. We have evaluated the effects of transcainide on sodium channel current in guinea pig ventricular myocytes using the whole-cell patch-clamp technique. Reduction of sodium current by transcainide was concentration dependent, with an ED50 of approximately 0.5 microM (n = 9). This reduction of the sodium current exhibited little use dependence, and block did not accumulate even after 10-Hz pulse trains. Moreover, little or no recovery from block was observed even when cells were hyperpolarized to -160 mV for 1 min. We observed no reversal of sodium channel block after superfusing cells up to 1 h in drug-free solution. Thus, transcainide, unlike many other clinically useful antiarrhythmic agents, blocked sodium channels with very little time dependence or voltage dependence. These novel electrophysiological properties of transcainide may endow the agent with a unique spectrum of efficacy against certain arrhythmias. At the same time, the great potency of transcainide and its lack of reversibility, at least within an hour, mandate that the drug should be used with great caution.