title: Control of sensory neuron excitability by serotonin involves 5HT2C receptors and Ca(2+)-activated chloride channels.
abstract: Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron. Unlike other algogenic mediators, such as PGE2 and bradykinin, 5HT did not affect currents through TTX-resistant Na(+) channels or Kv7 K(+) channels. In all neurons investigated, 5HT potentiated capsaicin-evoked currents through TRPV1 channels, an effect that was attenuated by antagonists at 5HT2A (4 F 4 PP), 5HT2B (SB 204741), as well as 5HT2C (RS 102221) receptors. 5HT triggered slowly arising inward Cl(-) currents in 53% of the neurons. This effect was antagonized by the 5HT2C receptor blocker only, and the current was prevented by an inhibitor of Ca(2+)-activated chloride channels (CaCC). The 5HT-induced increase in action potential firing was also abolished by this CaCC blocker and by the TRPV1 inhibitor capsazepine. Amongst the subtype selective 5HT2 antagonists, only RS 102221 (5HT2C-selectively) counteracted the rise in action potential firing elicited by 5HT. These results show that 5HT excites DRG neurons mainly via 5HT2C receptors which concomitantly mediate a sensitization of TRPV1 channels and an opening of CaCCs.
authors: Centre for Physiology and Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090 Vienna, Austria.
authors: Isabella
authors: I
authors: Salzer
authors: Centre for Physiology and Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090 Vienna, Austria.
authors: Enkhbileg
authors: E
authors: Gantumur
authors: Centre for Physiology and Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090 Vienna, Austria.
authors: Arsalan
authors: A
authors: Yousuf
authors: Centre for Physiology and Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090 Vienna, Austria. Electronic address: stefan.boehm@meduniwien.ac.at.
authors: Stefan
authors: S
authors: Boehm
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D051656:KCNQ Potassium Channels / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D051656:KCNQ Potassium Channels; D018377:Neurotransmitter Agents; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012701:Serotonin
keywords: 5HT2 receptors; Ca(2+)-activated chloride channels; Dorsal root ganglion neurons; Kv7 K(+) channels; TRPV1 channels; TTX-resistant Na(+) channels