Identification of Three Subunits of the High Affinity ω-Conotoxin MVIIC-sensitive Ca2+ Channel

N-, P- and Q-type voltage-dependent Ca2+ channels control neurotransmitter release in the nervous system and are blocked by omega-conotoxin MVIIC. In this study, both a high affinity and a low affinity binding site for omega-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 omega-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 alpha1A, alpha2delta, and any one of the four brain beta subunits. Such association of different beta subunits with alpha1A and alpha2delta components may produce Ca2+ channels with distinct functional properties, such as P- and Q-type.