Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics.
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.
Sirois
J E
JE
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. jes8q@virginia.edu
Pancrazio
J J
JJ
Lynch
C
C
Bayliss
D A
DA
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D002586:Cesium / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D007473:Ion Channels; D002586:Cesium; D001464:Barium; D011188:Potassium; D006221:Halothane