Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons

Br J Pharmacol. 2005 Jan;144(1):98-107. doi: 10.1038/sj.bjp.0705942.


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. 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 microM, close to the estimated clinical EC(50) (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 Ca(2+) channels, thiopental (25 microM) 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 approximately 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 EC(50) were also shown to inhibit nAChR-induced increases in [Ca(2+)](i) by approximately 40%. Thiopental (25 muM) 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. Depolarization-activated Ca(2+) channel currents were unaffected in the presence of thiopental (25 microM), pentobarbital (50 microM) and ketamine (10 microM). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Anesthetics, Dissociative / pharmacology
  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Animals, Newborn
  • Barbiturates / pharmacology
  • Calcium / metabolism*
  • Cells, Cultured
  • Electric Conductivity
  • Fluorescent Dyes
  • Fura-2
  • Ganglia, Parasympathetic / cytology
  • Ganglia, Parasympathetic / metabolism*
  • Ganglia, Parasympathetic / physiology
  • Heart / innervation*
  • Ketamine / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Pentobarbital / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / physiology
  • Thiopental / pharmacology


  • Anesthetics, Dissociative
  • Anesthetics, Intravenous
  • Barbiturates
  • Fluorescent Dyes
  • Receptors, Nicotinic
  • Ketamine
  • Pentobarbital
  • Thiopental
  • Acetylcholine
  • Calcium
  • Fura-2