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.
Romey
G
G
Centre de Biochimie du Centre National de la Recherche Scientifique, Nice, France.
Garcia
L
L
Rieger
F
F
Lazdunski
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D017275:Isradipine; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010069:Oxadiazoles; D010880:Piperidines; D013843:Thiazines; C055625:Hoe 166; C043184:4-desmethoxyverapamil; D014700:Verapamil; D017275:Isradipine