Halothane hyperpolarizes motoneurons at clinically relevant concentrations. A, Dark-field photomicrograph of emulsion-dipped section hybridized with a [³³P]-labeled cRNA probe specific to TASK-1. Note the high density of silver grains overlaying neurons in the hypoglossal nucleus (nXII); labeling is also apparent in the vagal motor nucleus (dmnX). Scale bar, 250 μm.B, Current-clamp recording of a hypoglossal motoneuron exposed to halothane (1.25 mm) and then to an acidified extracellular solution, pH 6.5, in the continued presence of halothane. Note that halothane caused a membrane hyperpolarization that was reversed by acidosis. The resting potential of the motoneuron was −73 mV; it was induced to fire repetitively under control conditions by current injection (360 pA, DC; action potentials are truncated by the chart recorder). C, Current-clamp recording of membrane potential in a hypoglossal motoneuron exposed to increasing concentrations of halothane. Membrane hyperpolarization was evident even at 0.1 mm and increased further in a concentration-dependent manner. The hyperpolarization induced by halothane was reversed when the acidified bath solution was introduced during halothane exposure. Control membrane potential in this motoneuron (and all cells tested with this protocol) was set at −60 mV by DC current injection. D,Concentration–response curves for membrane effects of halothane. The halothane-induced hyperpolarization from −60 mV was measured in individual cells exposed to multiple concentrations of halothane. Averaged data (± SEM) were plotted as a function of the aqueous concentrations of halothane solution (± SEM), determined from gas chromatographic analysis of replicate samples taken from the point of presentation to the slice. Data were well fitted with the logistic equation: ΔE_m = max ΔE_m/(1 + ([halothane]/EC₅₀)ⁿ), with an EC₅₀ of 260 μm, a Hill coefficient (n) of −2.9, and a maximum hyperpolarization (max ΔE_m) of 13 mV.Inset, Input conductance determined at each halothane concentration was normalized to control input conductance (G halothane/G control) and fitted to a logistic equation of similar form, with an EC₅₀ of 220 μm, n of −3.3, and a maximum G halothane/G control of 1.5 (i.e., 50% increase in conductance).