Reconstitution of Solubilized and Purified Dihydropyridine Receptor from Skeletal Muscle Microsomes as Two Single Calcium Channel Conductances with Different Functional Properties

Calcium entry through voltage-sensitive calcium channels (VSCC) is a vital link between membrane depolarization and cellular function (Hille 1984). In many excitable cells, the entry of Ca2+ ions can be inhibited by phenylalkylamines such as verapamil, D600, or D888; the benzodiazepine diltiazem; dihydropyridine (DHP) compounds such as nifedipine, nitrendipine, nimodipine, or PN200-110; and so on (Fleckenstein et al. 1985; Lichtlen 1985; Miller 1987a; Venter and Triggle 1987; Bechem and Schramm 1988; Pelzer et al. 1988). These drugs are often grouped together as Ca2+ antagonists (Fleckenstein 1977) or Ca2+ -channel blockers (Katz and Reuter 1979), although they represent quite different classes of organic compounds. As therapeutic agents in clinical medicine, they have proven effective in the treatment of cardiovascular disorders (Braunwald 1985). As ligands that bind to different but interacting sites on VSCC with high affinity and specificity, radiolabeled compounds out of each major class have taken the place of natural toxins as molecular probes to count, purify, and characterize VSCC (Catterall 1986; Fosset and Lazdunski 1987; Glossmann et al. 1987).