Acceleration of activation and inactivation by the β subunit of the skeletal muscle calcium channel

• Published in: Nature (London) Vol. 352; no. 6331; pp. 159 - 162
• Main Authors: Varadi, Gyula, Lory, Philippe, Schultz, David, Varadi, Maria, Schwartz, Arnold
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 11.07.1991
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Analytical, structural and metabolic biochemistry; Animals; Barium - metabolism; Binding and carrier proteins; Binding Sites; Biological and medical sciences; calcium; Calcium Channels - genetics; Calcium Channels - physiology; Cell Line; Cell Membrane - metabolism; Dihydropyridines - metabolism; DNA - genetics; Electric Conductivity; Fundamental and applied biological sciences. Psychology; Gene Expression; Ion Channel Gating; Isradipine; Kinetics; L Cells (Cell Line); Macromolecular Substances; Muscles - physiology; Oxadiazoles - metabolism; Proteins; Rabbits; Receptors, Nicotinic - physiology; Transfection; Vertebrata; Mammalia; Transfection; Calcium; Complementary DNA; Blotting assay; Electrophysiology; Activation; Ionic channel; Ionic current; Gene expression; Striated muscle
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/352159a0

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.