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

1 Halothane has many effects on the resting membrane potential (V-m) of exc itable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca2+ release by the sarcoplasmic reticulum (SR) resulti ng in a sustained contracture. The aim of this study was to analyse the eff ects of clinical doses of halothane on V-m, recorded using intracellular mi croelectrodes on cleaned and non stimulated sartorius muscle which was fres hly isolated from the leg of the frog Rana esculenta. 2 We assessed the mechanism of effects of superfused halothane on V-m by th e administration of selective antagonists of membrane bound Na+, K+ and Cl- channels and by inhibition of SR Ca2+ release. 3 Halothane (3%) induced an early and transient depolarization (4.5 mV with in 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of V-m. 4 The halothane-induced transient depolarization was sensitive to ryanodine (10 mu M) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic ac id (SITS, 1 mM). 5 The hyperpolarization of V, induced by halothane (0.1-3%) was dose-depend ent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 mu M), and tetraethylammonium (10 mM) but was blocked and/or prevented by rya nodine (10 mu M), charybdotoxin (CTX, 1 mu M), and glibenclamide (10 nM). 6 Our observations revealed that the effects of halothane on V-m may be rel ated to the increase in intracellular Ca2+ concentration produced by the ry anodine-sensitive Ca2+ release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca2+-dependent Cl- (b locked by SITS) channels and the hyperpolarization to the activation of lar ge conductance Ca2+-dependent K+ channels, blocked by CTX, and to the openi ng of ATP-sensitive K+ channels, inhibited by glibenclamide.