Journal Article

Inhibitory effects of intravenous anaesthetic agents on K+‐evoked norepinephrine and dopamine release from rat striatal slices: possible involvement of P/Q‐type voltage‐sensitive Ca2+ channels

K. Hirota, M. Kudo, T. Kudo, A. Matsuki and D. G. Lambert

in BJA: British Journal of Anaesthesia

Published on behalf of the British Journal of Anaesthesia

Volume 85, issue 6, pages 874-880
Published in print December 2000 | ISSN: 0007-0912
Published online December 2000 | e-ISSN: 1471-6771 | DOI: https://dx.doi.org/10.1093/bja/85.6.874
Inhibitory effects of intravenous anaesthetic agents on K+‐evoked norepinephrine and dopamine release from rat striatal slices: possible involvement of P/Q‐type voltage‐sensitive Ca2+ channels

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The role of the voltage‐sensitive Ca2+ channel (VSCC) as a target for anaesthetic action remains controversial. In this study we characterized the VSCC subtypes involved in K+‐evoked norepinephrine and dopamine release from rat striatal slices and used this model system to examine the effects of a range of i.v. anaesthetics on release. Nifedipine (L‐channel‐selective), ω‐conotoxin GVIA (N‐channel‐selective), ω‐agatoxin IVA (P‐channel‐selective), ω‐conotoxin MVIIC (P/Q‐channel‐selective) and Cd2+ (non‐selective), along with alphaxalone, propofol and ketamine, were used in various combinations. ω‐Agatoxin IVA, ω‐conotoxin MVIIC and Cd2+ fully (100%) inhibited norepinephrine and dopamine release. Clinically achievable concentrations of alphaxalone inhibited norepinephrine and dopamine release, with concentrations producing 25 and 50% inhibition (IC25 and IC50) of the maximum of 2.1 and 7.8 µM respectively for norepinephrine and 2.9 and 7.2 µM for dopamine. The effects of propofol were observed at the top of the clinical range and those of ketamine exceeded this range. In addition, IC50 values for alphaxalone in the presence and absence of nifedipine and ω‐conotoxin GVIA did not differ from the control. Our data suggest that clinically achievable concentrations of alphaxalone and propofol inhibit norepinephrine and dopamine release, which is mediated predominantly through P/Q‐type VSCCs, suggesting a role for these channels in anaesthetic action.

Br J Anaesth 2000; 85: 874–80

Keywords: Keywords: anaesthetics, i.v.; rat

Journal Article.  3633 words.  Illustrated.

Subjects: Anaesthetics

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