Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

Freisinger, Wolfgang; Schatz, Johannes; Ditting, Tilmann; Lampert, Angelika; Heinlein, Sonja; Lale, Nena; Schmieder, Roland E.; Veelken, Roland

doi:10.1152/ajprenal.00011.2012

Cited by 11 publications

(30 citation statements)

References 44 publications

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“…For instance, renal neurons exhibited sustained action potential (AP) firing upon stimulation with depolarizing current injections (tonic response pattern). We also showed that this firing pattern was related to an increased expression of specific subgroups of voltage-gated sodium channels, namely Nav1.7, Nav1.8, and Nav1.9 (13). Expression of voltage-gated sodium channels is sensitive to inflammatory conditions.…”

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confidence: 67%

“…Therefore, we hypothesized that inflammatory chemokines (6, 37) alter neuro-and electrophysiological properties of renal afferent nerves. We previously established an in vitro model of renal sensory afferent nerves by cultivating respective dorsal root ganglion (DRG) neurons in primary cell culture (10,13) to investigate neuronal mechanisms that cannot be tested by single or multifiber recording in vivo (15,41). We demonstrated that neurons with afferent axon projections to the kidney were distinctively different from neurons with axon projections to other sites (10).…”

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confidence: 99%

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Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1

Ditting

Freisinger

Rodionova

et al. 2016

American Journal of Physiology-Renal Physiology

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Recently, we showed that renal afferent neurons exhibit a unique firing pattern, i.e., predominantly sustained firing, upon stimulation. Pathological conditions such as renal inflammation likely alter excitability of renal afferent neurons. Here, we tested whether the proinflammatory chemokine CXCL1 alters the firing pattern of renal afferent neurons. Rat dorsal root ganglion neurons (Th11-L2), retrogradely labeled with dicarbocyanine dye, were incubated with CXCL1 (20 h) or vehicle before patchclamp recording. The firing pattern of neurons was characterized as tonic, i.e., sustained action potential (AP) firing, or phasic, i.e., Ͻ5 APs following current injection. Of the labeled renal afferents treated with vehicle, 58.9% exhibited a tonic firing pattern vs. 7.8%, in unlabeled, nonrenal neurons (P Ͻ 0.05). However, after exposure to CXCL1, significantly more phasic neurons were found among labeled renal neurons; hence the occurrence of tonic neurons with sustained firing upon electrical stimulation decreased (35.6 vs. 58.9%, P Ͻ 0.05). The firing frequency among tonic neurons was not statistically different between control and CXCL1-treated neurons. However, the lower firing frequency of phasic neurons was even further decreased with CXCL1 exposure [control: 1 AP/600 ms (1-2) vs. CXCL1: 1 AP/600 ms (1-1); P Ͻ 0.05; median (25th-75th percentile)]. Hence, CXCL1 shifted the firing pattern of renal afferents from a predominantly tonic to a more phasic firing pattern, suggesting that CXCL1 reduced the sensitivity of renal afferent units upon stimulation. chemokine; CXCL1; renal afferent nerve; voltage-gated sodium channel; tonic; phasic; firing pattern OBSERVATIONS IN PATIENTS with renal failure and/or hypertension who were nephrectomized (7, 17) strongly suggest that renal sensory afferent innervation increases sympathetic-mediated vasoconstriction. Moreover, sympathetic nerve activity in patients after renal transplantation was only normalized with concomitant bilateral nephrectomy (17). Additional work in experimental models indicated (21, 23) that efferent neurogenic influences on cardiac pathology in renal insufficiency are mediated by renal afferent nerve activity (1).In experimental animals, afferent innervation of the kidney was reported to contribute to the sustained blood pressure increases when renal structural damage was present (3, 46). In contrast, renal afferent nerves were described to act protectively against salt-sensitive hypertension and the structural renal damage of high blood pressure (24,44). A more recent study using a more selective method of renal afferent denervation suggests that this might not be the case, but it could be shown that selective renal afferent denervation was able to blunt the development of deoxycorticosterone acetate-salt hypertension (12).Therefore, the benefit of afferent renal nerve ablation for the treatment of refractory hypertension remains controversial (31). In any case, the modulatory influence of afferent renal nerves on sympathetic tone is not well understood....

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confidence: 67%

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confidence: 99%

Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1

Ditting

Freisinger

Rodionova

et al. 2016

American Journal of Physiology-Renal Physiology

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“…In some cases, authors have adopted the same criteria described above for sympathetic neurons (e.g., Ditting et al 2009;Yu et al 2014). Other authors used a more strict criteria for phasic neurons based on the number of APs fired during a continuous suprathreshold simulation, with phasic neurons firing exactly one (Chen et al 1987) or, at most, four APs (Sculptoreanu and de Groat 2007;Freisinger et al 2013). Neurons that fired more than these limits were classified as tonic cells.…”

Section: Action Potential Firing Patternsmentioning

confidence: 99%

“…For example, 90% of DRG neurons innervating the bladder are phasic (Kanda et al 2016), and capsaicin-sensitive bladder afferents change their firing pattern from phasic to tonic after spinal transection (Takahashi et al 2013). Similarly, Freisinger et al (2013) showed that a higher percentage of renal afferents are tonic (56%) compared to nonrenal afferents (12%). In mechanosensitive DRG neurons, neurons with Bnociceptive-like^APs were equally likely to have tonic or phasic responses, while neurons with Bnonnociceptive-like^APs are almost all phasic (ViatchenkoKarpinski and Gu 2016).…”

Section: Functional Relationships Associated With Tonic and Phasic Fimentioning

confidence: 99%

“…Retrograde labeling allows characterization of the neurons that innervate specific organs. In some special cases, where the sensory modality is known a priori, this approach allows the study of a functionally defined population (Benson et al 1999;Silbert et al 2003;Connor et al 2005;Freisinger et al 2013;Kanda et al 2016). In addition, genetically modified animals that express a marker (for example, a fluorescent protein) under the control of a gene of interest are useful tools to study the properties of neurons that express that gene (Dussor et al 2008;Tang et al 2016;Le Pichon and Chesler 2014).…”

Section: Introductionmentioning

confidence: 99%

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Morphological and functional diversity of first-order somatosensory neurons

2017

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First-order somatosensory neurons transduce and convey information about the external or internal environment of the body to the central nervous system. They are pseudo unipolar neurons with cell bodies residing in one of several ganglia located near the central nervous system, with the short branch of the axon connecting to the spinal cord or the brain stem and the long branch extending towards the peripheral organ they innervate. Besides their sensory transducer and conductive role, somatosensory neurons also have trophic functions in the tissue they innervate and participate in local reflexes in the periphery. The cell bodies of these neurons are remarkably diverse in terms of size, molecular constitution, and electrophysiological properties. These parameters have provided criteria for classification that have proved useful to establish and study their functions. In this review, we discuss ways to measure and classify populations of neurons based on their size and action potential firing pattern. We also discuss attempts to relate the different populations to specific sensory modalities.

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Neurogenic substance P—influences on action potential production in afferent neurons of the kidney?

Rodionova

Hilgers

Linz

et al. 2021

Pflugers Arch - Eur J Physiol

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We recently showed that a substance P (SP)–dependent sympatho-inhibitory mechanism via afferent renal nerves is impaired in mesangioproliferative nephritis. Therefore, we tested the hypothesis that SP released from renal afferents inhibits the action potential (AP) production in their dorsal root ganglion (DRG) neurons. Cultured DRG neurons (Th11-L2) were investigated in current clamp mode to assess AP generation during both TRPV1 stimulation by protons (pH 6) and current injections with and without exposure to SP (0.5 µmol) or CGRP (0.5 µmol). Neurons were classified as tonic (sustained AP generation) or phasic (≤ 4 APs) upon current injection; voltage clamp experiments were performed for the investigation of TRPV1-mediated inward currents due to proton stimulation. Superfusion of renal neurons with protons and SP increased the number of action potentials in tonic neurons (9.6 ± 5 APs/10 s vs. 16.9 ± 6.1 APs/10 s, P < 0.05, mean ± SD, n = 7), while current injections with SP decreased it (15.2 ± 6 APs/600 ms vs. 10.2 ± 8 APs/600 ms, P < 0.05, mean ± SD, n = 29). Addition of SP significantly reduced acid-induced TRPV1-mediated currents in renal tonic neurons (− 518 ± 743 pA due to pH 6 superfusion vs. − 82 ± 50 pA due to pH 6 with SP superfusion). In conclusion, SP increased action potential production via a TRPV1-dependent mechanism in acid-sensitive renal neurons. On the other hand, current injection in the presence of SP led to decreased action potential production. Thus, the peptide SP modulates signaling pathways in renal neurons in an unexpected manner leading to both stimulation and inhibition of renal neuronal activity in different (e.g., acidic) environmental contexts.

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Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

Cited by 11 publications

References 44 publications

Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1

Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1

Morphological and functional diversity of first-order somatosensory neurons

Neurogenic substance P—influences on action potential production in afferent neurons of the kidney?

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