Pharmacological evidence for an omega-conotoxin, dihydropyridine-insensitive neuronal Ca2+ channel

• Published in: European journal of pharmacology Vol. 206; no. 1; p. 61
• Main Authors: Lundy, P M, Frew, R, Fuller, T W, Hamilton, M G
• Format: Journal Article
• Language: English
• Published: Netherlands 25-01-1991
• Subjects: Acetylcholine - metabolism; Animals; Cadmium - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Chickens; Choline - metabolism; Dihydropyridines - pharmacology; In Vitro Techniques; Luminescent Measurements; Male; Nerve Tissue Proteins - metabolism; Neurons - drug effects; Neurons - metabolism; omega-Conotoxin GVIA; Peptides, Cyclic - pharmacology; Rats; Rats, Inbred Strains; Synaptosomes - drug effects; Synaptosomes - metabolism; Veratridine - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0922-4106(91)90147-A

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.