Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics

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 (E(K)) 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 E(K). 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 I(h), 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 I(h) activation. Extracellular Cs+ (3 mM) blocked I(h) and a component of halothane-sensitive current with properties reminiscent of I(h). 5. A small component of halothane current, resistant to Ba2+ and Cs+, was observed in TTX-containing solutions at potentials depolarized to ~ -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 I(h) 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.