Do distinct populations of dorsal root ganglion neurons account for the sensory peptidergic innervation of the kidney?

Ditting T, Tiegs G, Rodionova K, Reeh PW, Neuhuber W, Freisinger W, Veelken R. Do distinct populations of dorsal root ganglion neurons account for the sensory peptidergic innervation of the kidney? Am J Physiol Renal Physiol 297: F1427-F1434, 2009. First published August 19, 2009; doi:10.1152/ajprenal.90599.2008.-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 generelated 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.