Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel.
The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current.
Varadi
G
G
Department of Pharmacology and Cell Biophysics, University of Cincinnati, Ohio 45267-0575.
Lory
P
P
Schultz
D
D
Varadi
M
M
Schwartz
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D001665:Binding Sites; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004095:Dihydropyridines / Q000378:metabolism; D004553:Electric Conductivity; D015870:Gene Expression; D015640:Ion Channel Gating; D017275:Isradipine; D007700:Kinetics; D007739:L Cells; D046911:Macromolecular Substances; D009132:Muscles / Q000502:physiology*; D010069:Oxadiazoles / Q000378:metabolism; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000502:physiology; D014162:Transfection
D015220:Calcium Channels; D004095:Dihydropyridines; D046911:Macromolecular Substances; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D004247:DNA; D017275:Isradipine