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J Neurophysiol 86: 241-248, 2001;
0022-3077/01 $5.00
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The Journal of Neurophysiology Vol. 86 No. 1 July 2001, pp. 241-248
Copyright ©2001 by the American Physiological Society

5HT Increases Excitability of Nociceptor-Like Rat Dorsal Root Ganglion Neurons Via cAMP-Coupled TTX-Resistant Na+ Channels

Luz M. Cardenas, Carla G. Cardenas, and Reese S. Scroggs

Department of Anatomy and Neurobiology, Health Science Center, University of Tennessee, Memphis, Tennessee 38163

Cardenas, Luz M., Carla G. Cardenas, and Reese S. Scroggs. 5HT Increases Excitability of Nociceptor-Like Rat Dorsal Root Ganglion Neurons Via cAMP-Coupled TTX-Resistant Na+ Channels. J. Neurophysiol. 86: 241-248, 2001. 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 µM 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 µM) 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.




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