STRUCTURE AND FUNCTIONAL EXPRESSION OF ALPHA-1-SUBUNIT, ALPHA-2-SUBUNIT, AND BETA-SUBUNIT OF A NOVEL HUMAN NEURONAL CALCIUM-CHANNEL SUBTYPE

The primary structures of human neuronal alpha-1, alpha-2, and beta-subunits of a voltage-dependent Ca2+ channel were deduced by characterizing cDNAs. The alpha-subunit (alpha-1D) directs the recombinant expression of a dihydropyridine-sensitive L-type Ca2+ channel when coexpressed with the beta-(beta-2) and the alpha-2 (alpha-2b) subunits in Xenopus oocytes. The recombinant channel is also reversibly blocked by 10-15-mu-M omega-conotoxin. Expression of the alpha-1D Subunit alone, or coexpression with the alpha-2b subunit, did not elicit functional Ca2+ channel activity. Thus, the beta-2 subunit appears to serve an obligatory function, whereas the alpha-2b subunit appears to play an accessory role that potentiates expression of the channel. The primary transcripts encoding the alpha-1D, alpha-2, and beta-subunits are differentially processed. At least two forms of neuronal alpha-1D were identified. Different forms of alpha-2 and beta-transcripts were also identified in CNS, skeletal muscle, and aorta tissues.