Neurokinins enhance excitability in capsaicin-responsive DRG neurons

• Published in: Experimental neurology Vol. 205; no. 1; pp. 92 - 100
• Main Authors: Sculptoreanu, Adrian, de Groat, William C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2007; Elsevier
• Subjects: Action Potentials - drug effects; Animals; Autofeedback; Biological and medical sciences; Capsaicin - pharmacology; Development. Senescence. Regeneration. Transplantation; Dorsal root ganglia; Electric Stimulation; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - physiology; Hyperexcitability; Intracellular Membranes - metabolism; Isolated neuron and nerve. Neuroglia; K + channels; Male; Neurokinin A - analogs & derivatives; Neurokinin A - pharmacology; Neurokinins; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Nociception; Patch-Clamp Techniques; Peptide Fragments - pharmacology; Potassium Channel Blockers - pharmacology; Potassium Channels - physiology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Protein Kinase Inhibitors - pharmacology; Rats; Receptors, Neurokinin-2 - antagonists & inhibitors; Receptors, Neurokinin-2 - metabolism; Signal Transduction; Substance P - pharmacology; Tachykinins - physiology; Vertebrates: nervous system and sense organs; Nociception; Dorsal root ganglia; K + channels; Neurokinins; Autofeedback; Hyperexcitability; Spinal cord; Protein kinase C; Rat; Capsaicin; Central nervous system; Electrophysiology; Action potential; Ionic current; Neuropeptide; Signal transduction; Neurokinin A; Enzyme; Substance P; Transferases; Rodentia; Excitability; cAMP-dependent protein kinase; Long term; Vertebrata; Mammalia; Clamping(surgery); Neuron; Protein kinase; Animal; K+ channels; NK2 Tachykinin receptor; Spinal ganglion; Intracellular; Technique; Tachykinin; Patch; Potassium
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2007.01.038

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 μM) 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 II (0.05 μM) or low concentrations of 4-aminopyridine (50 μM) that block A-type K + currents. A selective NK 2 agonist, [βAla 8]-neurokinin A (4–10) (0.5 μM), mimicked the effects of SP. The effects of SP in C-R phasic neurons were fully reversed by an NK 2 receptor antagonist (MEN10376, 0.5  μM) but only partially by a protein kinase C (PKC) inhibitor (bisindolylmaleimide, 0.5 μM). An NK 3-selective agonist ([MePhe 7]-neurokinin B, 0.5 μM), an NK 1-selective agonist ([Sar 9, Met 11]-substance P, 0.5 μM) or activation of PKC with phorbol 12,13-dibutyrate (0.5 μM) did not change firing. Our data suggest that the excitability of C-R phasic afferent neurons is increased by activation of NK 2 receptors and intracellular signaling mediated only in part by PKC.