Ketamine blockade of voltage-gated sodium channels - Evidence for a sharedreceptor site with local anesthetics

Citation
Le. Wagner et al., Ketamine blockade of voltage-gated sodium channels - Evidence for a sharedreceptor site with local anesthetics, ANESTHESIOL, 95(6), 2001, pp. 1406-1413
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ANESTHESIOLOGY
ISSN journal
0003-3022 → ACNP
Volume
95
Issue
6
Year of publication
2001
Pages
1406 - 1413
Database
ISI
SICI code
0003-3022(200112)95:6<1406:KBOVSC>2.0.ZU;2-7
Abstract
Background: The general anesthetic ketamine is known to be an N-methyl-D-as partate receptor blocker. Although ketamine also blocks voltage-gated sodiu m channels in a local anesthetic-like fashion, little Information exists on the molecular pharmacology of this interaction. We measured the effects of ketamine on sodium channels. Methods: Wild-type and mutant (F1579A) recombinant rat skeletal muscle sodi um channels were expressed in Xenopus oocytes. The F1579A amino acid substi tution site is part of the intrapore local anesthetic receptor. The effect of ketamine was measured in oocytes expressing wild-type or mutant sodium c hannels using two-electrode voltage clamp. Results: Ketamine blocked sodium channels in a local anesthetic-like fashio n, exhibiting tonic blockade (concentration for half-maximal inhibition [IC 50] = 0.8 mM), phasic blockade (IC50 = 2.3 mm), and leftward shift of the s teady-state inactivation; the parameters of these actions were strongly mod ified by alteration of the intrapore local anesthetic binding site (IC50 = 2.1 nim and IC50 = 10.3 mM for tonic and phasic blockade, respectively). Co mpared with lidocaine, ketamine showed greater tonic inhibition but less ph asic blockade. Conclusions: Ketamine interacts with sodium channels in a local anesthetic- like fashion, including sharing a binding site with commonly used clinical local anesthetics.