Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons
Article first published online: 29 JAN 2009
2005 British Pharmacological Society
British Journal of Pharmacology
Volume 144, Issue 1, pages 98–107, January 2005
How to Cite
Weber, M., Motin, L., Gaul, S., Beker, F., Fink, R. H. A. and Adams, D. J. (2005), Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons. British Journal of Pharmacology, 144: 98–107. doi: 10.1038/sj.bjp.0705942
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received May 19, 2004, Revised June 28, 2004, Accepted July 8, 2004)
- Intracardiac ganglia;
- ganglionic transmission;
- nicotinic acetylcholine receptor;
- intracellular Ca2+;
- intravenous anaesthetics;
- 1The 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.
- 2In 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.
- 3In 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.
- 4The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC50 were also shown to inhibit nAChR-induced increases in [Ca2+]i by ∼40%.
- 5Thiopental (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.
- 6Depolarization-activated Ca2+ channel currents were unaffected in the presence of thiopental (25 μM), pentobarbital (50 μM) and ketamine (10 μM).
- 7In 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