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 microM, 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 microM, 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-à-go-go K+ current, and an inward rectifier K+ current, with a respective IC50 of 0.3, 0.7 and 5.6 microM. 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.
Liu
J H
JH
Département de Physiologie, Centre Médical Universitaire, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Bijlenga
P
P
Occhiodoro
T
T
Fischer-Lougheed
J
J
Bader
C R
CR
Bernheim
L
L
D000293:Adolescent; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002459:Cell Fusion / Q000187:drug effects; D004558:Electric Stimulation; D006801:Humans; D007223:Infant; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D020748:Mibefradil; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015221:Potassium Channels; D013764:Tetrahydronaphthalenes; D020748:Mibefradil