Structure and functional expression of α₁, α₂, and β subunits of a novel human neuronal calcium channel subtype

The primary structures of human neuronal α₁, α₂, and β subunits of a voltage-dependent Ca²⁺ channel were deduced by characterizing cDNAs. The α₁ subunit (α_1D) directs the recombinant expression of a dihydropyridine-sensitive L-type Ca²⁺ channel when coexpressed with the β (β₂) and the α₂ (α_2b) subunits in Xenopus oocytes. The recombinant channel is also reversibly blocked by 10-15 μM ω-conotoxin. Expression of the α_1D subunit alone, or coexpression with the α_2b subunit, did not elicit functional Ca²⁺ channel activity. Thus, the β₂ subunit appears to serve an obligatory function, whereas the α_2b subunit appears to play an accessory role that potentiates expression of the channel. The primary transcripts encoding the α_1D, α₂, and β subunits are differentially processed. At least two forms of neuronal α_1D were identified. Different forms of α₂ and β transcripts were also identified in CNS, skeletal muscle, and aorta tissues.