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Keywords:

  • Intracardiac ganglia;
  • ganglionic transmission;
  • nicotinic acetylcholine receptor;
  • intracellular Ca2+;
  • intravenous anaesthetics;
  • thiopental;
  • pentobarbital;
  • ketamine;
  • caffeine
  • 1
    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.
  • 2
    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.
  • 3
    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.
  • 4
    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%.
  • 5
    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.
  • 6
    Depolarization-activated Ca2+ channel currents were unaffected in the presence of thiopental (25 μM), pentobarbital (50 μM) and ketamine (10 μM).
  • 7
    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