Journal
EXPERIMENTAL NEUROLOGY
Volume 205, Issue 1, Pages 92-100Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2007.01.038
Keywords
dorsal root ganglia; nociception; hyperexcitability; K channels; neurokinins; autofeedback
Categories
Funding
- NIDDK NIH HHS [R37 DK049430, R37 DK049430-06] Funding Source: Medline
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Neurokinins released by capsaicin-responsive (C-R) dorsal root ganglia neurons (DRG) may control firing in these neurons by an autofeedback mechanism. Here we used patch clamp techniques to examine the effects of neurokinins on firing properties of dissociated DRG neurons of male rats. In C-R neurons that generated only a few action potentials (APs, termed phasic) in response to long depolarizing current pulses (600 ms), substance P (SP, 0.5 mu M) lowered the AP threshold by 11.0 +/- 0.3 mV and increased firing from 1.1 +/- 0.7 APs to 5.2 +/- 0.6 APs. In C-R tonic neurons that fire multiple APs, SP elicited smaller changes in AP threshold (6.0 +/- 0.1 mV reduction) and the number of APs (11 +/- 1 vs. 9 +/- 1 in control). The effects of SP were similar to the effect of heteropodatoxin 11 (0.05 mu M) or low concentrations of 4-aminopyridine (50 mu M) that block A-type K+ currents. A selective NK2 agonist, [beta A(8)]-neurokinin A (4-10) (0.5 mu M), mimicked the effects of SP. The effects of SP in C-R phasic neurons were fully reversed by an NK2 receptor antagonist (MEN10376, 0.5 mu M) but only partially by a protein kinase C (PKC) inhibitor (bisindolylmaleimide, 0.5 mu M). An NK3-selective agonist ([MePhe(7)]-neurokinin B, 0.5 mu M), an NK1-selective agonist ([Sar(9), Met(11)]-substance P, 0.5 mu M) or activation of PKC with phorbol 12,13-dibutyrate (0.5 mu M) did not change firing. Our data suggest that the excitability of GR phasic afferent neurons is increased by activation of NK2 receptors and intracellular signaling mediated only in part by PKC. (C) 2007 Elsevier Inc. All rights reserved.
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