Effects of halothane on the membrane potential in skeletal muscle of the frog

Abstract : Halothane has many effects on the resting membrane potential (Vm) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca2+ release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical doses of halothane on Vm, recorded using intracellular microelectrodes on cleaned and non stimulated sartorius muscle which was freshly isolated from the leg of the frog Rana esculenta. We assessed the mechanism of effects of superfused halothane on Vm by the administration of selective antagonists of membrane bound Na+, K+ and Cl− channels and by inhibition of SR Ca2+ release. Halothane (3%) induced an early and transient depolarization (4.5 mV within 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of Vm. The halothane-induced transient depolarization was sensitive to ryanodine (10 μm) and to 4-acetamido-4′-isothiocyanatostilbene 2,2′ disulphonic acid (SITS, 1 mm). The hyperpolarization of Vm induced by halothane (0.1-3%) was dose-dependent and reversible. It was insensitive to SITS (1 mm), tetrodotoxin (0.6 μm), and tetraethylammonium (10 mm) but was blocked and/or prevented by ryanodine (10 μm), charybdotoxin (CTX, 1 μm), and glibenclamide (10 nm). Our observations revealed that the effects of halothane on Vm may be related to the increase in intracellular Ca2+ concentration produced by the ryanodine-sensitive Ca2+ release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca2+-dependent Cl− (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca2+-dependent K+ channels, blocked by CTX, and to the opening of ATP-sensitive K+ channels, inhibited by glibenclamide.
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Submitted on : Wednesday, July 3, 2013 - 3:14:13 PM
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Martin-Pierre Sauviat, H.-P. Frizelle, A. Descorps-Declère, J.-X. Mazoit. Effects of halothane on the membrane potential in skeletal muscle of the frog. British Journal of Pharmacology, Wiley, 2000, 130 (3), pp.619-624. ⟨10.1038/sj.bjp.0703330⟩. ⟨hal-00838174⟩

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