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We examined the effects of equianesthetic concentrations of sevoflurane, desflurane, isoflurane, and halothane on the spontaneous contractility of isolated human pregnant uterine muscles. We also determined if their action was related to potassium channels. Uterine specimens were obtained from normal full-term pregnant women undergoing elective lower-segment cesarean delivery. Longitudinal muscle strips were mounted vertically in tissue chambers. Their isometric tension was recorded while they were exposed to 0.5-3 minimum alveolar concentration (MAC) of volatile anesthetics in the absence and presence of the high conductance calcium-activated potassium channel blocker, tetraethylammonium, or the adenosine triphosphate-sensitive potassium channel (K(ATP))-blocker, glibenclamide. The anesthetics examined produced a dose-dependent depression of contractility. The inhibitory potency of sevoflurane and desflurane was comparable to, whereas that of isoflurane was smaller than, that of halothane: concentrations causing 50% inhibition of the contractile amplitude (ED(50)) were 1.72, 1.44, 2.35, and 1.66 MAC (P < 0.05), respectively. Tetraethylammonium and glibenclamide did not affect the uterine response to the anesthetics, except for glibenclamide, which attenuated the response to isoflurane. These results indicate that the volatile anesthetics have inhibitory effects on the contractility of the human uterus. The inhibitory effect of isoflurane may in part be mediated through activation of K(ATP) channels.