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Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation anaesthetics
Author(s) -
Sirois Jay E.,
Pancrazio Joseph J.,
Lynch Carl,
Bayliss Douglas A.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.851bd.x
Subject(s) - halothane , chemistry , isoflurane , biophysics , hyperpolarization (physics) , voltage clamp , anesthetic , anesthesia , membrane potential , acetylcholine , pharmacology , biochemistry , stereochemistry , medicine , biology , organic chemistry , nuclear magnetic resonance spectroscopy
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 Ba 2+ (2 m m ). Moreover, the Ba 2+ ‐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 Ba 2+ ‐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 m m ) 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 Ba 2+ 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 Ba 2+ ‐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.