IDENTIFICATION OF 1,4-DIHYDROPYRIDINE BINDING DOMAINS WITHIN THE PRIMARY STRUCTURE OF THE ALPHA-1 SUBUNIT OF THE SKELETAL-MUSCLE L-TYPE CALCIUM-CHANNEL

Calcium channel blockers are drugs that bind to the alpha1 subunit of L-type calcium channels and selectively inhibit ion movements through these channels. Determination of the mechanism of channel blockade requires localization of drug-binding sites within the primary structure of the receptor. In this study the 1,4-dihydropyridine-binding site of the membrane bound receptor has been identified. The covalently labeled receptor was purified and digested with trypsin. The labeled peptide fragments were immunoprecipitated with sequence-directed antibodies. The data indicate the existence of at least three distinct dihydropyridine-binding domains within the primary structure of the alpha1 subunit.