Mibefradil (Ro 40‐5967) inhibits several Ca 2+ and K + currents in human fusion‐competent myoblasts

The effect of mibefradil (Ro 40–5967), an inhibitor of T‐type Ca 2+ current (I Ca(T) ), on myoblast fusion and on several voltage‐gated currents expressed by fusion‐competent myoblasts was examined. At a concentration of 5 μ M , mibefradil decreases myoblast fusion by 57%. At this concentration, the peak amplitudes of I Ca(T) and L‐type Ca 2+ current (I Ca(L) ) measured in fusion‐competent myoblasts are reduced by 95 and 80%, respectively. The IC 50 of mibefradil for I Ca(T) and I Ca(L) are 0.7 and 2 μ M , respectively. At low concentrations, mibefradil increased the amplitude of I Ca(L) with respect to control. 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 IC 50 of 0.3, 0.7 and 5.6 μ M . 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 Ca 2+ currents.British Journal of Pharmacology (1999) 126 , 245–250; doi: 10.1038/sj.bjp.0702321