Effects of Serotonin on Caudal Raphe Neurons: Activation of an Inwardly Rectifying Potassium Conductance

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Abstract
Bayliss, Douglas A., Yu-Wen Li, and Edmund M. Talley. Effects of serotonin on caudal raphe neurons: activation of an inwardly rectifying potassium conductance. J. Neurophysiol. 77: 1349–1361, 1997. We used whole cell current- and voltage-clamp recording in neonatal rat brain stem slices to characterize firing properties and effects of serotonin (5-HT) on neurons( n = 225) in raphe pallidus (RPa) and raphe obscurus (ROb). Of a sample of 51 Lucifer yellow-filled neurons recovered after immunohistochemical processing to detect tryptophan hydroxylase (TPH), 34 were found to be TPH immunoreactive (i.e., serotonergic). Serotonergic neurons had long-duration action potentials and fired spontaneously at low frequency (∼1 Hz) in a pattern that was often irregular; at higher firing frequencies the discharge became more regular. These neurons displayed spike frequency adaptation, with maximal steady-state firing rates of +. It was completely blocked by 0.2 mM Ba2+ but not by glibenclamide, an inhibitor of ATP-sensitive K+ channels. Effects of 5-HT were dose dependent, with an EC50 of 0.1–0.3 μM. The 5-HT1A agonist 8-OH-DPAT mimicked, and the 5-HT1A antagonists (+)WAY 100135 and NAN 190 blocked, effects of 5-HT. The 5-HT2A/C antagonist ketanserin did not inhibit the effects of 5-HT. Fewer 5-HT-responsive neurons were encountered in slices exposed acutely to pertussis toxin (∼13%) than in adjacent control slices not exposed to pertussis toxin (∼85%). In addition, in neurons recorded with pipettes containing GTPγS (0.1 mM), 5-HT induced an inwardly rectifying current that did not reverse on washing. In many cells recorded with GTPγS, a current developed in the absence of agonist that had properties identical to those of the 5-HT-sensitive current; when followed for extended periods, the agonist-independent GTPγS-induced conductance desensitized, returning toward control levels with a time constant of ∼18 min. Together these results indicate that serotonergic neurons of ROb and RPa are spontaneously active in a neonatal rat brain stem slice preparation and that hyperpolarization of those neurons by 5-HT1A receptor stimulation is due to pertussis toxin-sensitive G protein-mediated activation of an inwardly rectifying K+ conductance. In addition, we identified a group of nonserotonergic medullary raphe neurons that had distinct electrophysiological properties and that was depolarized by 5-HT.