5-HYDROXYTRYPTAMINE EVOKES DEPOLARIZATIONS AND MEMBRANE-POTENTIAL OSCILLATIONS IN RAT SYMPATHETIC PREGANGLIONIC NEURONES

1. Whole-cell recordings were made from seventy-seven identified rat s ympathetic preganglionic neurones (SPN) in spinal cord slices. Perfusi on of 5-HT (0.5-30 mu M) strongly depolarized 90% of neurones. The res ponse was slow in onset, could last over 10 min and was associated wit h an increase in input resistance. 5-HT could also evoke rhythmical me mbrane potential oscillations in a population of previously quiescent neurones. 2. The 5-HT response persisted in TTX and also in low-Ca2+-h igh-Mg2+ artificial cerebrospinal fluid (ACSF), suggesting that the re ceptors are on SPN. The 5-HT uptake inhibitor 6-nitroquipazine potenti ated the 5-HT-induced depolarization. 3. The 5-HT-induced depolarizati on was reduced and then abolished by membrane hyper polarization to po tentials of about -100 mV, but was not reversed in sign by further hyp erpolarization. In voltage clamp, 5-HT evoked inward currents associat ed with the reduction of an outwardly rectifying potassium conductance . 4. The 5-HT, receptor agonist alpha-methyl-5-HT mimicked the 5-HT re sponse on all neurones, as did the 5-HT, receptor agonist 5-carboxamid otryptamine (5-CT) on 71% of SPN, The responses to 5-HT, alpha-methyl- 5-HT and 5-HT were inhibited by the 5-HT, antagonists ketanserin and r itanserin. 5. Pressure ejection of 5-HT over the central canal region could evoke a biphasic inhibitory-excitatory response. This response p ersisted in TTX, suggesting that an inhibitory 5-HT receptor may be lo cated on the medial dendrites. 6. SPN are powerfully depolarized by 5- HT acting at 5-HT, receptors, via the closure of an outwardly rectifyi ng potassium conductance. The long duration of the response and the ab ility of 5-HT to induce rhythmical oscillations suggest that 5-HT may have an important role in regulating SPN excitability.