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- Title
Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca<sup>2+</sup> transients in rat intracardiac ganglion neurons.
- Authors
Weber, Martin; Motin, Leonid; Gaul, Simon; Beker, Friederike; Fink, Rainer H. A.; Adams, David J.
- Abstract
The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-induced transients in intracellular free Ca2+ concentration ([Ca2+]i) and membrane currents were investigated in neonatal rat intracardiac neurons.In fura-2-loaded neurons, nAChR activation evoked a transient increase in[Ca2+]I, which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The half-maximal concentration for thiopental inhibition of nAChR-induced[Ca2+]i transients was 28?µM, close to the estimated clinical EC50 (clinically relevant (half-maximal) effective concentration) of thiopental.In fura-2-loaded neurons, voltage clamped at-60?mV to eliminate any contribution of voltage-gated Ca2+ channels, thiopental (25?µM) simultaneously inhibited nAChR-induced increases in[Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialysed whole-cell recordings by~40%at-120,-80 and-40?mV holding potential, indicating that the inhibition is voltage independent.The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC50 were also shown to inhibit nAChR-induced increases in[Ca2+]i by~40%.Thiopental (25?µM) did not inhibit caffeine-, muscarine- or ATP-evoked increases in[Ca2+]i, indicating that inhibition of Ca2+ release from internal stores via either ryanodine receptor or inositol-1,4,5-trisphosphate receptor channels is unlikely.Depolarization-activated Ca2+ channel currents were unaffected in the presence of thiopental (25?µM), pentobarbital (50?µM) and ketamine (10?µM).In conclusion, i.v. anaesthetics inhibit nAChR-induced currents and[Ca2+]i transients in intracardiac neurons by binding to nAChRs and thereby may contribute to changes in heart rate and cardiac output under clinical conditions.British Journal of Pharmacology (2005) 144, 98-107. doi:10.1038/sj.bjp.0705942
- Publication
British Journal of Pharmacology, 2005, Vol 144, Issue 1, p98
- ISSN
0007-1188
- Publication type
Academic Journal
- DOI
10.1038/sj.bjp.0705942