Omega-conotoxin GVIA binding to a high-affinity receptor in brain: characterization, calcium sensitivity, and solubilization.
We describe unique, high-affinity binding sites for omega[125I]conotoxin GVIA in membranes from rat brain and rabbit sympathetic ganglia which appear to be primarily associated with N-type voltage-dependent calcium channels. The dissociation constant (KD) for the toxin in rat brain membranes is 60 pM. Physiologic extracellular concentrations of calcium inhibit toxin binding noncompetitively (IC50 = 0.2 mM). The regional distribution of the binding sites in rat brain differs markedly from that of dihydropyridine calcium antagonist receptors associated with L-type calcium channels. In detergent-solubilized brain membranes, toxin binding retains the same affinity, specificity, and ionic sensitivity as in particulate preparations.
Wagner
J A
JA
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Snowman
A M
AM
Biswas
A
A
Olivera
B M
BM
Snyder
S H
SH
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels; D002412:Cations / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008978:Mollusk Venoms / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012995:Solubility; D014018:Tissue Distribution; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D002412:Cations; D007457:Iodine Radioisotopes; D008978:Mollusk Venoms; D010455:Peptides; D017981:Receptors, Neurotransmitter; C053157:omega-conotoxin receptor; D020866:omega-Conotoxin GVIA; D002118:Calcium