Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics

JE Sirois, JJ Pancrazio, C Lynch III… - The Journal of …, 1998 - Wiley Online Library
JE Sirois, JJ Pancrazio, C Lynch III, DA Bayliss
The Journal of physiology, 1998Wiley Online Library
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 …
  • 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 ∼−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.
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