The primary structures of human neuronal al, a2, and B subunits of a voltage-dependent Caz+ channel were deduced by characterizing cDNAs. The al subunit (aID) directs the recombinant expression of a dihydropyridinesensitive l-type Caz+ channel when coexpressed with the g (gZ) and the a2 (a2b) subunits in Xenopus oocytes. The recombinant channel is also reversibly blocked by 10-15 uM o-conotoxin. Expression of the ulDsubunit alone, or coexpression with the azb subunit, did not elicit functional Ca*+ channel activity. Thus, the g2 subunit appears to serve an obligatory function, whereas the a2b subunit appears to play an accessory role that potentiates expression of the channel. The primary transcripts encoding the aID, a2, and/3 subunits are differentially processed. At least two forms of neuronal ulD were identified. Different forms of a2 and B transcripts were also identified in CNS, skeletal muscle, and aorta tissues.