Targets for calcium channel blockers in mammalian skeletal muscle and their respective functions in excitation-contraction coupling.

The L-type Ca2+ channel is blocked by 1,4-dihydropyridines (DHP), by phenylalkylamines, by diphenylbutylpiperidines or by benzolactams. We first show with mouse muscle cells in culture that all these L-type Ca2+ channel blockers block contraction. However, voltage-clamp analysis associated to contraction measurements also clearly show that Ca2+ influx through L-type Ca2+ channels is not required for contraction. Therefore, there is a need for a voltage-sensor which would be responsible for the excitation-contraction (E-C) coupling. We are showing here that the voltage-sensor involved in E-C coupling and the L-type Ca2+ channel have a similar pharmacology. Some of the blockers used are more active on the voltage sensor, others on the L-type Ca2+ channel.