MOLECULAR-CLONING OF THE ALPHA-1 SUBUNIT OF AN OMEGA-CONOTOXIN-SENSITIVE CALCIUM-CHANNEL

Of the four major types of Ca channel described in vertebrate cells (designated T, L, N, and P), N-type Ca channels are unique in that they are found specifically in neurons, have been correlated with control of neurotransmitter release, and are blocked by omega-conotoxin, a neuropeptide toxin isolated from the marine snail Conus geographus. A set of overlapping cDNA clones were isolated and found to encode a Ca channel alpha-1 subunit, designated rbB-I. Polyclonal antiserum generated against a peptide from the rbB-I sequence selectively immunoprecipitates high-affinity I-125-labeled omega-conotoxin-binding sites from labeled rat forebrain membranes. PCR analysis shows that, like N-type Ca channels, expression of rbB-I is limited to the nervous system and neuronally derived cell lines. This brain Ca channel may mediate the omega-conotoxin-sensitive Ca influx required for neurotransmitter release at many synapses.