title: Do distinct populations of dorsal root ganglion neurons account for the sensory peptidergic innervation of the kidney?
abstract: Peptidergic afferent renal nerves (PARN) have been linked to kidney damage in hypertension and nephritis. Neither the receptors nor the signals controlling local release of neurokinines [calcitonin gene-related peptide (CGRP) and substance P (SP)] and signal transmission to the brain are well-understood. We tested the hypothesis that PARN, compared with nonrenal afferents (Non-RN), are more sensitive to acidic stimulation via transient receptor potential vanilloid type 1 (TRPV1) channels and exhibit a distinctive firing pattern. PARN were distinguished from Non-RN by fluorescent labeling (DiI) and studied by in vitro patch-clamp techniques in dorsal root ganglion neurons (DRG; T11-L2). Acid-induced currents or firing due to current injection or acidic superfusion were studied in 252 neurons, harvested from 12 Sprague-Dawley rats. PARN showed higher acid-induced currents than Non-RN (transient: 15.9 +/- 5.1 vs. 0.4 +/- 0.2* pA/pF at pH 6; sustained: 20.0 +/- 4.5 vs. 6.2 +/- 1.2* pA/pF at pH 5; *P < 0.05). The TRPV1 antagonist capsazepine inhibited sustained, amiloride-transient currents. Forty-eight percent of PARN were classified as tonic neurons (TN = sustained firing during current injection), and 52% were phasic (PN = transient firing). Non-RN were rarely tonic (15%), but more frequently phasic (85%), than PARN (P < 0.001). TN were more frequently acid-sensitive than PN (50-70 vs. 2-20%, P < 0.01). Furthermore, renal PN were more frequently acid-sensitive than nonrenal PN (20 vs. 2%, P < 0.01). Confocal microscopy revealed innervation of renal vessels, tubules, and glomeruli by CGRP- and partly SP-positive fibers coexpressing TRPV1. Our data show that PARN are represented by a very distinct population of small-to-medium sized DRG neurons exhibiting more frequently tonic firing and TRPV1-mediated acid sensitivity. These very distinct DRG neurons might play a pivotal role in renal physiology and disease.
authors.affiliation: Department of Internal Medicine 4, Nephrology, and Hypertension, University of Erlangen, Nuremberg, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Ditting
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.forename: Kristina
authors.initials: K
authors.lastname: Rodionova
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reeh
authors.forename: Winfried
authors.initials: W
authors.lastname: Neuhuber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Freisinger
authors.forename: Roland
authors.initials: R
authors.lastname: Veelken
mesh_terms: D062565:Acid Sensing Ion Channels; D000143:Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007668:Kidney / Q000294:innervation*; D007672:Kidney Cortex / Q000294:innervation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology
chemical_list: D062565:Acid Sensing Ion Channels; D000143:Acids; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat