Intravenous anaesthetics inhibit nicotinic acetylcholine receptor‐mediated currents and Ca 2+ transients in rat intracardiac ganglion neurons

1 The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)‐induced transients in intracellular free Ca 2+ concentration ([Ca 2+ ] i ) and membrane currents were investigated in neonatal rat intracardiac neurons. 2 In fura‐2‐loaded neurons, nAChR activation evoked a transient increase in [Ca 2+ ] I , which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The half‐maximal concentration for thiopental inhibition of nAChR‐induced [Ca 2+ ] i transients was 28  μ M , close to the estimated clinical EC 50 (clinically relevant (half‐maximal) effective concentration) of thiopental. 3 In fura‐2‐loaded neurons, voltage clamped at −60 mV to eliminate any contribution of voltage‐gated Ca 2+ channels, thiopental (25  μ M ) simultaneously inhibited nAChR‐induced increases in [Ca 2+ ] 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. 4 The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC 50 were also shown to inhibit nAChR‐induced increases in [Ca 2+ ] i by ∼40%. 5 Thiopental (25  μ M ) did not inhibit caffeine‐, muscarine‐ or ATP‐evoked increases in [Ca 2+ ] i , indicating that inhibition of Ca 2+ release from internal stores via either ryanodine receptor or inositol‐1,4,5‐trisphosphate receptor channels is unlikely. 6 Depolarization‐activated Ca 2+ channel currents were unaffected in the presence of thiopental (25  μ M ), pentobarbital (50  μ M ) and ketamine (10  μ M ). 7 In conclusion, i.v. anaesthetics inhibit nAChR‐induced currents and [Ca 2+ ] 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