Mibefradil (Ro 40-5967) inhibits several Ca²⁺and K⁺currents in human fusion-competent myoblasts

1 The effect of mibefradil (Ro 40-5967), an inhibitor of T-type Ca2+ current (I-Ca(T)), on myoblast fusion and on several voltage-gated currents expressed by fusion-competent myoblasts was examined. 2 At a concentration of 5 mu M, mibefradil decreases myoblast fusion by 57%. At this concentration, the peak amplitudes of I-Ca(T) and L-type Ca2+ current (I-Ca(L)) measured in fusion-competent myoblasts are reduced by 95 and 80%, respectively. The IC50 of mibefradil for I-Ca(T) and I-Ca(L) are 0.7 and 2 mu M, respectively. 3 At low concentrations, mibefradil increased the amplitude of I-Ca(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-a-go-go K+ current, and an inward rectifier K+ current, with a respective IC50 of 0.3, 0.7 and 5.6 mu M. 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.