Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics

J Physiol. 1998 Nov 1;512 ( Pt 3)(Pt 3):851-62. doi: 10.1111/j.1469-7793.1998.851bd.x.

Abstract

1. We studied the effects of inhalation anaesthetics on the membrane properties of hypoglossal motoneurones in a neonatal rat brainstem slice preparation. 2. In current clamp, halothane caused a membrane hyperpolarization that was invariably associated with decreased input resistance; in voltage clamp, halothane induced an outward current and increased input conductance. Qualitatively similar results were obtained with isoflurane and sevoflurane. 3. The halothane current reversed near the predicted K+ equilibrium potential (EK) and was reduced in elevated extracellular K+ and in the presence of Ba2+ (2 mM). Moreover, the Ba2+-sensitive component of halothane current was linear and reversed near EK. The halothane current was not sensitive to glibenclamide or thyrotropin-releasing hormone (TRH). Therefore, the halothane current was mediated, in part, by activation of a Ba2+-sensitive K+ current distinct from the ATP- and neurotransmitter-sensitive K+ currents in hypoglossal motoneurones. 4. Halothane also inhibited Ih, a hyperpolarization-activated cationic current; this was primarily due to a decrease in the absolute amount of current, although halothane also caused a small, but statistically significant, shift in the voltage dependence of Ih activation. Extracellular Cs+ (3 mM) blocked Ih and a component of halothane-sensitive current with properties reminiscent of Ih. 5. A small component of halothane current, resistant to Ba2+ and Cs+, was observed in TTX-containing solutions at potentials depolarized to approximately -70 mV. Partial Na+ substitution by N-methyl-D-glucamine completely abolished this residual current, indicating that halothane also inhibited a TTX-resistant Na+ current active near rest potentials. 6. Thus, halothane activates a Ba2+-sensitive, relatively voltage-independent K+ current and inhibits both Ih and a TTX-insensitive persistent Na+ current in hypoglossal motoneurones. These effects of halothane decrease motoneuronal excitability and may contribute to the immobilization that accompanies inhalation anaesthesia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Animals, Newborn
  • Barium / pharmacology
  • Brain Stem / cytology
  • Brain Stem / physiology
  • Cesium / pharmacology
  • Electric Stimulation
  • Electrophysiology
  • Halothane / pharmacology
  • Hypoglossal Nerve / cytology
  • Hypoglossal Nerve / drug effects
  • Hypoglossal Nerve / physiology
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Membrane Potentials / physiology
  • Motor Neurons / drug effects*
  • Patch-Clamp Techniques
  • Potassium / physiology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anesthetics, Inhalation
  • Ion Channels
  • Cesium
  • Barium
  • Potassium
  • Halothane