Serotinin (5-HT) induced a slow depolarization when superfused onto neurons of the rat brainstem nucleus prepositus hypoglossi (PH) in vitro. The depolarization was associated with a decrease in cell input resistance. In voltage clamp, 5-HT caused an inward current that activated at approximately -50 mV and was present only at potentials negative to this. With hyperpolarizing voltage-clamp steps, PH neurons exhibited a slow inward current relaxation. The properties of this conductance were consistent with the cationic, nonselective current, Ih Bath-applied 5-HT augmented Ih. Extracellular CsCI blocked both Ih and the inward current produced by 5-HT. In addition, forskolin, isobutylmethylxanthine, and 8-bromo-CAMP mimicked the inward current seen with 5-HT. The 5-HT1 agonist 5-carboxamidotryptamine produced a similar inward current. We conclude that 5-HT excites PH neurons by augmenting Ih, probably through receptor-mediated stimulation of adenylate cyclase. As Ih is found in many types of neurons, this mechanism may be a common mode of regulating cell excitability.
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