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

TY - JOUR

T1 - Do distinct populations of dorsal root ganglion neurons account for the sensory peptidergic innervation of the kidney?

AU - Ditting, Tilmann

AU - Tiegs, Gisa

AU - Rodionova, Kristina

AU - Reeh, Peter W

AU - Neuhuber, Winfried

AU - Freisinger, Wolfgang

AU - Veelken, Roland

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 297

SP - 1427

EP - 1434

JO - AM J PHYSIOL-RENAL

JF - AM J PHYSIOL-RENAL

SN - 1931-857X

IS - 5

M1 - 5

ER -