5HT increases excitability of nociceptor-like rat dorsal root ganglion neurons via cAMP-coupled TTX-resistant Na(+) channels

J Neurophysiol. 2001 Jul;86(1):241-8. doi: 10.1152/jn.2001.86.1.241.

Abstract

The physiological effects of 5HT receptor coupling to TTX-resistant Na(+) current, and the signaling pathway involved, was studied in a nociceptor-like subpopulation of rat dorsal root ganglion (DRG) cells (type 2), which can be identified by expression of a low-threshold, slowly inactivating A-current. The 5HT-mediated increase in TTX-resistant Na(+) current in type 2 DRG cells was mimicked and occluded by 10 microM forskolin. Superfusion of type 2 DRG cells on the outside with 1 mM 8-bromo-cAMP or chlorophenylthio-cAMP (CPT-cAMP) increased the Na(+) current, but less than 5HT itself. However, perfusion of the cells inside with 2 mM CPT-cAMP strongly increased the amplitude of control Na(+) currents and completely occluded the effect of 5HT. Thus it appears that the signaling pathway includes cAMP. The phosphodiesterase inhibitor 3-isobutyl-L-methylxanthine (200 microM) also mimicked the effect of 5HT on Na(+) current, suggesting tonic adenylyl cyclase activity. 5HT reduced the amount of current required to evoke action potentials in type 2 DRG cells, suggesting that 5HT may lower the threshold for activation of nociceptor peripheral receptors. The above data suggest that serotonergic modulation of TTX-resistant Na(+) channels through a cAMP-dependent signaling pathway in nociceptors may participate in the generation of hyperalgesia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism*
  • Cyclic AMP / pharmacology
  • Free Radical Scavengers / pharmacology*
  • Ganglia, Spinal / cytology*
  • Hyperalgesia / metabolism
  • Male
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Nociceptors / drug effects*
  • Nociceptors / physiology
  • Potassium / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / pharmacology*
  • Sodium / metabolism
  • Sodium Channels / metabolism*
  • Tetrodotoxin / physiology
  • Thionucleotides / pharmacology

Substances

  • Free Radical Scavengers
  • Sodium Channels
  • Thionucleotides
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Serotonin
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Tetrodotoxin
  • Sodium
  • Cyclic AMP
  • Potassium