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

Halothane has many effects on the resting membrane potential (V m ) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca 2+ 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 V m , 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 V m by the administration of selective antagonists of membrane bound Na + , K + and Cl − channels and by inhibition of SR Ca 2+ 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 V m . The halothane‐induced transient depolarization was sensitive to ryanodine (10 μ M ) and to 4‐acetamido‐4′‐isothiocyanatostilbene 2,2′ disulphonic acid (SITS, 1 m M ). The hyperpolarization of V m induced by halothane (0.1–3%) was dose‐dependent and reversible. It was insensitive to SITS (1 m M ), tetrodotoxin (0.6 μ M ), and tetraethylammonium (10 m M ) but was blocked and/or prevented by ryanodine (10 μ M ), charybdotoxin (CTX, 1 μ M ), and glibenclamide (10 n M ). Our observations revealed that the effects of halothane on V m may be related to the increase in intracellular Ca 2+ concentration produced by the ryanodine‐sensitive Ca 2+ release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca 2+ ‐dependent Cl − (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca 2+ ‐dependent K + channels, blocked by CTX, and to the opening of ATP‐sensitive K + channels, inhibited by glibenclamide.British Journal of Pharmacology (2000) 130 , 619–624; doi: 10.1038/sj.bjp.0703330