Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HT4 receptors and cAMP-dependent mechanisms.

Neuropharmacology
Elia R LopezEdgar T Walters

Abstract

Ongoing activity in nociceptors, a driver of spontaneous pain, can be generated in dorsal root ganglion neurons in the absence of sensory generator potentials if one or more of three neurophysiological alterations occur - prolonged depolarization of resting membrane potential (RMP), hyperpolarization of action potential (AP) threshold, and/or increased amplitude of depolarizing spontaneous fluctuations of membrane potential (DSFs) to bridge the gap between RMP and AP threshold. Previous work showed that acute, sustained exposure to serotonin (5-HT) hyperpolarized AP threshold and potentiated DSFs, leading to ongoing activity if a separate source of maintained depolarization was present. Cellular signaling pathways that increase DSF amplitude and promote ongoing activity acutely in nociceptors are not known for any neuromodulator. Here, isolated DRG neurons from male rats were used to define the pathway by which low concentrations of 5-HT enhance DSFs, hyperpolarize AP threshold, and promote ongoing activity. A selective 5-HT4 receptor antagonist blocked these 5-HT-induced hyperexcitable effects, while a selective 5-HT4 agonist mimicked the effects of 5-HT. Inhibition of cAMP effectors, protein kinase A (PKA) and exchange protei...Continue Reading

References

Jan 1, 1992·Neuroscience·Y O Taiwo, J D Levine
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·M S GoldJ D Levine
Jan 22, 2003·Neuroscience Letters·R NicholsonK Lee
Mar 4, 2003·Journal of Neurophysiology·M SchmelzH O Handwerker
Feb 12, 2004·Bioinformatics·M J L de HoonS Miyano
Jan 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Laiche DjouhriSally N Lawson
Mar 30, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jin-Ah KimJung-Ha Lee
Jul 1, 2006·Anesthesiology·Stephen E AbramQuinn H Hogan
Sep 5, 2008·Current Protocols in Cytometry·Mario Roederer
Apr 8, 2009·Experimental Brain Research·Aliakmal Momin, Peter A McNaughton
Nov 5, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Supinder S BediEdgar T Walters
Jan 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shih-Yuan LinWei-Hsin Sun
Sep 10, 2011·Science·Edward C EmeryPeter A McNaughton
Sep 25, 2012·Seminars in Cell & Developmental Biology·Dayna R LoydKenneth M Hargreaves
Jan 5, 2013·Journal of Medicinal Chemistry·Haijun ChenJia Zhou
Nov 25, 2014·Nature Neuroscience·Dmitry UsoskinPatrik Ernfors
Aug 14, 2015·Journal of Neurophysiology·D P FieldsG S Mitchell
Jul 18, 2016·NeuroImage·Tim GodelPhilipp Bäumer
Jun 6, 2017·Molecular Pain·Li-Yen Huang, Yanping Gu
Apr 5, 2018·The Journal of Cell Biology·Jörg IsenseeTim Hucho
Mar 14, 2019·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Peng PanSu Cao
Mar 20, 2019·Brain : a Journal of Neurology·Robert Y NorthPatrick M Dougherty
Jul 10, 2019·Science Advances·Saad S NagiHåkan Olausson
Sep 24, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Edgar T Walters

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