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.