Pharmacological evidence for an omega-conotoxin, dihydropyridine-insensitive neuronal Ca2+ channel.
Inactivation of N-type voltage-sensitive Ca2+ channels (VSCC) with omega-conotoxin (omega-CgTx) in tissue obtained from chicken brain produces a concentration dependent (0.01-0.1 microM) inhibition of K(+)-stimulated Ca2+ influx (delta K+), the rise in [Ca2+]i and acetylcholine (ACh) release. In identical preparations from rat brain, Ca2+ influx and the rise in [Ca2+]i were only marginally affected by much higher (1-10 microM) concentrations of omega-CgTx. The release of ACh, however, was inhibited to the same degree with similar amounts of omega-CgTx as those used in chicken brain. An L-type VSCC inhibitor failed to affect any of these parameters alone, or to augment the effect of omega-CgTx. The results suggest that almost all the VSCC in chicken brain are of the N type and that these channels regulate neurotransmitter release. In rat brain, on the other hand, Ca2+ channels resistant to N- or L-type blockers account for almost 75% of the measurable Ca2+ influx and rise in [Ca2+]i. The conspicuous dissociation between the regulation of Ca2+ influx and ACh release demonstrated in rat brain by using omega-CgTx, suggest that neurotransmitter release is governed by only a small proportion of strategically located N-type, omega-CgTx sensitive, VSCC in the presynaptic terminal.
Lundy
P M
PM
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Frew
R
R
Fuller
T W
TW
Hamilton
M G
MG
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002645:Chickens; D002794:Choline / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D009419:Nerve Tissue Proteins; D010456:Peptides, Cyclic; D002104:Cadmium; D014701:Veratridine; D020866:omega-Conotoxin GVIA; D002794:Choline; D000109:Acetylcholine; D002118:Calcium