Identification of three subunits of the high affinity ω-conotoxin MVIIC-sensitive Ca 2 + channel

N-, P- and Q-type voltage-dependent Ca²⁺ channels control neurotransmitter release in the nervous system and are blocked by ω-conotoxin MVIIC. In this study, both a high affinity and a low affinity binding site for ω-conotoxin MVIIC were detected in rabbit brain. The low affinity binding site is shown to be present on the N-type Ca²⁺ channel. Using optimized conditions for specific labeling of the high affinity ω-conotoxin MVIIC receptor and a panel of subunit specific antibodies, the molecular structure of the high affinity receptor was investigated. We demonstrate for the first time that this receptor is composed of at least α_1A, α₂δ, and any one of the four brain β subunits. Such association of different β subunits with α_1A and α₂δ components may produce Ca²⁺ channels with distinct functional properties, such as P- and Q-type.