Pharmacological evidence for an ω-conotoxin, dihydropyridine-insensitive neuronal Ca 2+ channel

Abstract

Inactivation of N-type voltage-sensitive Ca 2+ channels (VSCC) with ω-conotoxin (ω-CgTx) in tissue obtained from chicken brain produces a concentration dependent (0.01–0.1 μM) inhibition of K −-stimulated Ca 2+ influx (ΔK +) the rise in [Ca 2+] 1 and acetylcholine (ACh) release. In identical preparations from rat brain, Ca 2+ influx and the rise in [Ca 2+] 1 were only marginally affected by much higher (1–10 μM) concentrations of ω-CgTx. The release of ACh, however, was inhibited to the same degree with similar amourts of ω-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 ω-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, Ca 2+ channels resistant to N- or L-type blockers account for almost 75% of the measurable Ca 2+ influx and rise in [Ca 2+] 1. The conspicuous dissociation between the regulation of Ca 2+ influx and ACh release demonstrated in rat brain by using ω-CgTx, suggest that neurotransmitter release is governed by only a small proportion of strategically located N-type, ω-CgTx sensitive. VSCC in the presynaptic terminal.