January 1999, Volume 126, Issue 1, Pages 245 - 250

Original Article

Mibefradil (Ro 40-5967) inhibits several Ca2+ and K+ currents in human fusion-competent myoblasts Jian-Hui Liu, Philippe Bijlenga, Teresa Occhiodoro, Jacqueline Fischer-Lougheed, Charles R. Bader & Laurent Bernheim1 Département de Physiologie, Centre Médical Universitaire, Division de Recherche Clinique Neuro-Musculaire, Hôpital Cantonal Universitaire, CH-1211 Geneva 4, Switzerland     1Author for correspondence at: Département de Physiologie, Centre Médical Universitaire, 1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland; E-mail: laurent.bernheim@medecine.unige.ch

Keywords

Myoblast;   potassium current;   mibefradil;   myoblast fusion

Abstract

1   The effect of mibefradil (Ro 40-5967), an inhibitor of T-type Ca2+ current (ICa(T)), on myoblast fusion and on several voltage-gated currents expressed by fusion-competent myoblasts was examined. 2   At a concentration of 5 µM, mibefradil decreases myoblast fusion by 57%. At this concentration, the peak amplitudes of ICa(T) and L-type Ca2+ current (ICa(L)) measured in fusion-competent myoblasts are reduced by 95 and 80%, respectively. The IC50 of mibefradil for ICa(T) and ICa(L) are 0.7 and 2 µM, respectively. 3   At low concentrations, mibefradil increased the amplitude of ICa(L) with respect to control. 4   Mibefradil blocked three voltage-gated K+ currents expressed by human fusion-competent myoblasts: a delayed rectifier K+ current, an ether-à-go-go K+ current, and an inward rectifier K+ current, with a respective IC50 of 0.3, 0.7 and 5.6 µM. 5   It is concluded that mibefradil can interfere with myoblast fusion, a mechanism fundamental to muscle growth and repair, and that the interpretation of the effect of mibefradil in a given system should take into account the action of this drug on ionic currents other than Ca2+ currents.

Received 27 August 1998; Revised 23 October 1998; Accepted 26 October 1998

^© Macmillan Publishers Ltd 1999