5-Hydoxytryptamine evokes depolarizations and membrane potential oscillations in rat sympathetic preganglionic neurones.
1. Whole-cell recordings were made from seventy-seven identified rat sympathetic preganglionic neurones (SPN) in spinal cord slices. Perfusion of 5-HT (0.5-30 microM) strongly depolarized 90% of neurones. The response was slow in onset, could last over 10 min and was associated with an increase in input resistance. 5-HT could also evoke rhythmical membrane potential oscillations in a population of previously quiescent neurones. 2. The 5-HT response persisted in TTX and also in low-Ca(2+)-high-Mg2+ artificial cerebrospinal fluid (ACSF), suggesting that the receptors are on SPN. The 5-HT uptake inhibitor 6-nitroquipazine potentiated the 5-HT-induced depolarization. 3. The 5-HT-induced depolarization was reduced and then abolished by membrane hyperpolarization to potentials of about -100 mV, but was not reversed in sign by further hyperpolarization. In voltage clamp, 5-HT evoked inward currents associated with the reduction of an outwardly rectifying potassium conductance. 4. The 5-HT2 receptor agonist alpha-methyl-5-HT mimicked the 5-HT response on all neurones, as did the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT) on 71% of SPN. The responses to 5-HT, alpha-methyl-5-HT and 5-CT were inhibited by the 5-HT2 antagonists ketanserin and ritanserin. 5. Pressure ejection of 5-HT over the central canal region could evoke a biphasic inhibitory-excitatory response. This response persisted in TTX, suggesting that an inhibitory 5-HT receptor may be located on the medial dendrites. 6. SPN are powerfully depolarized by 5-HT acting at 5-HT2 receptors, via the closure of an outwardly rectifying potassium conductance. The long duration of the response and the ability of 5-HT to induce rhythmical oscillations suggest that 5-HT may have an important role in regulating SPN excitability.
Department of Physiology, University of Birmingham, UK.
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Pickering
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Spanswick
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Logan
D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D015221:Potassium Channels; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors