High-threshold voltage-sensitive calcium channels of the N-type, L-type, and 
P-type have been distinguished in the mammalian CNS predominantly on the basis 
of their sensitivity to selective antagonists. Matching them with genes 
identified by molecular cloning is an ongoing undertaking. Whereas L-type 
channels are characterized by their sensitivity to dihydropyridines and P-type 
channels by sensitivity to the funnel-web spider toxin AgaIVA, the N-type 
channel has been shown to be recognized by the omega-conopeptides GVIA and 
MVIIA. Recently, two new members of the family of omega-conopeptides--MVIIC from 
the marine snail Conus magus and SVIB from Conus striatus--have been described. 
Binding and electrophysiological data suggest that these two peptides, in 
addition to interacting with N-type calcium channels, interact with a widely 
distributed receptor in neuronal membranes that is distinct from N-type 
channels. In this report we demonstrate through biochemical and pharmacological 
differentiation at individual receptor polypeptide resolution, by affinity 
cross-linking, SDS-PAGE, and autoradiography, that SNX-230 (synthetic MVIIC) 
binds with high affinity to a calcium channel alpha 1 subunit distinct from the 
high-affinity alpha 1 target of SNX-111 (synthetic MVIIA). SNX-183 (synthetic 
SVIB) interacts with both alpha 1 subunits with lower affinity. Whereas the 
alpha 1 subunit recognized with high affinity by MVIIA corresponds to the N-type 
channel, the other represents a novel calcium channel distinct from N-, L-, and 
perhaps P-type channels.