A slow excitatory postsynaptic potential mediated by 5-HT2 receptors in nucleus prepositus hypoglossi.
Intracellular recordings were made from neurons of the nucleus prepositus hypoglossi in slices of guinea pig medulla. 5-HT (serotonin) caused a hyperpolarization followed by a late depolarization. The hyperpolarization was mediated by 5-HT1A receptor activation and could be selectively blocked by pindobind-5HT1A (PBD). 5-HT then caused a depolarization only. A selective 5-HT2 agonist, (+)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), also caused a depolarization. Ketanserin and spiperone, 5-HT2 antagonists, blocked the depolarization due to both 5-HT and DOI. Focal electrical stimulation caused an IPSP mediated by 5-HT acting upon 5-HT1A receptors and a slow EPSP (s-EPSP). PBD blocked the IPSP, leaving an isolated s-EPSP. Both spiperone and ketanserin antagonized the s-EPSP, while DOI occluded it. The s-EPSP was from 2 to 10 mV in amplitude and 35-50 sec in duration, and showed voltage dependence consistent with a decrease in potassium conductance. Both the IPSP and the s-EPSP were presynaptically inhibited by the 5-HT1D agonist sumatriptan. These data indicate that the s-EPSP is mediated by 5-HT acting upon 5-HT2 receptors. This represents strong support for the role of 5-HT as an excitatory neurotransmitter in the CNS. Further, it demonstrates that synaptic release of 5-HT can mediate opposing effects on the membrane potential of a single cell.
Bobker
D H
DH
Department of Neurology, Vollum Institute, Oregon Health Science University, Portland 97201.
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D000081005:Cyclohexane Monoterpenes; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000662:Amphetamines; D000081005:Cyclohexane Monoterpenes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C084712:pindobind; D012701:Serotonin; D013134:Spiperone; D018170:Sumatriptan; D007650:Ketanserin; D010869:Pindolol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine