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 microM) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic acid (SITS, 1 mM). The hyperpolarization of V(m) induced by halothane (0.1 - 3%) was dose-dependent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 microM), and tetraethylammonium (10 mM) but was blocked and/or prevented by ryanodine (10 microM), charybdotoxin (CTX, 1 microM), and glibenclamide (10 nM). 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.
Sauviat
M P
MP
Ecole Polytechnique-ENSTA, Unité INSERM 451, Cheminde la Huniére, 91761 Palaiseau, France. sauviat@enstay.ensta.fr
Frizelle
H P
HP
Descorps-Declère
A
A
Mazoit
J X
JX
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D018482:Muscle, Skeletal / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D011893:Rana esculenta; D012433:Ryanodine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D018999:Charybdotoxin; D012433:Ryanodine; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D005905:Glyburide; D006221:Halothane