1 The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-induced transients in intracellular free Ca 2 þ concentration ([Ca 2 þ ] 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 þ ] I , which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The halfmaximal concentration for thiopental inhibition of nAChR-induced [Ca 2 þ ] i transients was 28 mM, close to the estimated clinical EC 50 (clinically relevant (half-maximal) effective concentration) of thiopental.3 In fura-2-loaded neurons, voltage clamped at À60 mV to eliminate any contribution of voltagegated Ca 2 þ channels, thiopental (25 mM) simultaneously inhibited nAChR-induced increases in [Ca 2 þ ] i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialysed whole-cell recordings by B 40% at À120, À80 and À40 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 þ ] i by B40%. 5 Thiopental (25 mM) did not inhibit caffeine-, muscarine-or ATP-evoked increases in [Ca 2 þ ] i , indicating that inhibition of Ca 2 þ release from internal stores via either ryanodine receptor or inositol-1,4,5-trisphosphate receptor channels is unlikely. 6 Depolarization-activated Ca 2 þ channel currents were unaffected in the presence of thiopental (25 mM), pentobarbital (50 mM) and ketamine (10 mM). 7 In conclusion, i.v. anaesthetics inhibit nAChR-induced currents and [Ca 2 þ ] i transients in intracardiac neurons by binding to nAChRs and thereby may contribute to changes in heart rate and cardiac output under clinical conditions.

No abstract