title: Serotonin upregulates low- and high-threshold tetrodotoxin-resistant sodium channels in the same subpopulation of rat nociceptors.
abstract: The modulation by serotonin (5-HT) of low- and high-threshold tetrodotoxin- (TTX) resistant Na(+) currents was studied in small-diameter (approximately 25 microm) acutely-isolated rat dorsal root ganglion (DRG) cells. Each DRG cell included in the study was classified as type 2 or non-type 2, based on expression of a low-threshold A-type K(+) current. When cells of either type were recorded from using a CsF based internal solution and a holding potential (HP) of -80 mV, the apparent threshold for activation of TTX-resistant Na(+) currents ranged from -75 to -60 mV. A 500 ms prepulse to -60 mV greatly suppressed currents evoked by test potentials (TPs) to -75 through -35 mV. A similar scenario was observed when the CsF based internal solution was changed for one that contained CsCl, except that the apparent threshold of activation was shifted by about +25 mV, and currents evoked by TPs to -55 to -35 mV in the absence of a prepulse were much smaller than their counterparts observed with the CsF internal. These data suggest two types of TTX-resistant Na(+) currents; one with a low-threshold for activation that is enhanced by the presence of fluoride inside the cell and is inactivated by holding at -60 mV, and one with a higher threshold for activation that is not inactivated by holding at -60 mV. In type 2 DRG cells, 10 microM 5-HT upregulated low-threshold currents evoked by TPs to -55 to -35 mV from HP -80 mV, as well as high-threshold currents evoked by more depolarized TPs from HP -60 mV. However, when cells were held at -60 mV, 5-HT did not upregulate currents evoked by TPs to -35 or -30 mV, suggesting that the low-threshold current was nearly completely inactivated. Previous studies have suggested that type 2 DRG cells are nociceptor cell bodies. If 5-HT produces similar effects in type 2 DRG cell peripheral receptors, the upregulation of the low-threshold currents may serve to lower the threshold for nociception, while the upregulation of the high-threshold current may strengthen nociceptive signals.
authors.affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38139, USA. rscroggs@utmem.edu
authors.forename: R S
authors.initials: RS
authors.lastname: Scroggs
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005459:Fluorides / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D002712:Chlorides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012701:Serotonin; D013779:Tetrodotoxin; D012964:Sodium; D005459:Fluorides; D011188:Potassium