Molecular studies of the calcium antagonist binding site on calcium channels.
Currently available calcium antagonists act primarily on L-type calcium channels. Composed of 5 subunits, this ion channel is markedly more complicated than the potassium and sodium channels. Most of the data that have emerged over the past year have concerned the alpha subunit. The secondary structure of this subunit includes 4 repeating motifs; each motif contains 6 membrane-spanning helices, designated S1 through S6. The dihydropyridine (e.g., nifedipine) binding site is most likely situated primarily in motif 4 and the phenylalkylamine (e.g., verapamil) binding site is on motif 4 in an intracellular region. The benzothiazepine (e.g., diltiazem) binding site is also located on the alpha 1 subunit, but its precise location has not been determined. The transmembrane helices S5 and S6 of each motif have been proposed as the "wall" of the actual ion channel.
Schwartz
A
A
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio.
D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000648:ultrastructure*; D018257:Helix-Loop-Helix Motifs; D006801:Humans
D002121:Calcium Channel Blockers; D015220:Calcium Channels