Reciprocal modulation of Ih and ITASK in thalamocortical relay neurons by halothane

By combining electrophysiological, immunohistochemical, and computer modeling techniques, we examined the effects of halothane on the standing outward current (ISO) and the hyperpolarization-activated current (Ih) in rat thalamocortical relay (TC) neurons of the dorsal lateral geniculate nucleus (dLGN). Hyperpolarizing voltage steps elicited an instantaneous current component (Ii) followed by a slower time-dependent current that represented Ih. Halothane reduced Ih by shifting the voltage dependency of activation toward more negative potentials and by reducing the maximal conductance. Moreover, halothane augmented Ii and ISO. During the blockade of Ih through Cs+, the current–voltage relationship of the halothane-sensitive current closely resembled the properties of a current through members of the TWIK-related acid-sensitive K+ (TASK) channel family (ITASK). Computer simulations in a single-compartment TC neuron model demonstrated that the modulation of Ih and ITASK is sufficient to explain the halothane-induced hyperpolarization of the membrane potential observed in current clamp recordings. Immunohistochemical staining revealed protein expression of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel proteins HCN1, HCN2, and HCN4. Together with the dual effect of halothane on Ih properties, these results suggest that Ih in TC neurons critically depends on HCN1/HCN2 heterodimers. It is concluded that the reciprocal modulation of Ih and ITASK is an important mechanism of halothane action in the thalamus.

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