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....
Freisinger W, Schatz J, Ditting T, Lampert A, Heinlein S, Lale N, Schmieder R, Veelken R. Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels? Am J Physiol Renal Physiol 304: F491-F497, 2013. First published January 2, 2013; doi:10.1152/ajprenal.00011.2012.-Sensory neurons with afferent axons from the kidney are extraordinary in their response to electrical stimulation. More than 50% exhibit a tonic firing pattern, i.e., sustained action potential firing throughout depolarizing, pointing to an increased excitability, whereas nonrenal neurons show mainly a phasic response, i.e., less than five action potentials. Here we investigated whether these peculiar firing characteristics of renal afferent neurons are due to differences in the expression of voltage-gated sodium channels (Na vs). Dorsal root ganglion (DRG) neurons from rats were recorded by the current-clamp technique and distinguished as "tonic" or "phasic. .67]; P Ͻ 0.05). These findings point to an increased presence of the TTX-resistant Na vs 1.8 and 1.9. Furthermore, tonic neurons exhibited a relatively higher portion of TTX-resistant sodium currents. Interestingly, mRNA expression of TTX-resistant sodium channels was significantly increased in renal, predominantly tonic, DRG neurons. Hence, under physiological conditions, renal sensory neurons exhibit predominantly a firing pattern associated with higher excitability. Our findings support that this is due to an increased expression and activation of TTX-resistant Na vs.
Zeitshrift fur alle Gebiete der Chemischen Technik und des Chemie-Ingenieurwesensi n F o r t f u h r u n g d e r Z e i t s c h r i f t , , A n g e w a n d t e C h e m i e " T e i l B ( f r u h e r , , D i e C h e m i s c h e T e c h n i k " ) u n d d e r , , B e i h e f t e V e r f a h r e n s t e c h n i k z u r V D I -Z e i t s c h r i f t " 25. 'Jabrganp Xr. 2 Stiff 61-112 3ebruar 1953 Edelmetall-Legierungen mit besonderer Bestandigkeit gegen starke Mineralsauren') Von J O H A N N E S SCHATZ, Degussa, Frankfurt am MainZum 80jahrigen Bestehen der Deutschen Gold-und Silber-Scheideansfalt vormals Roessler, Frankfurt a. M.Es werden zwei Gruppen von Edelmetall -Legier ungen beschrieben, die sich bereits seit langem Chemie-Ing.-Te&n. 25. Jahrg. 1953 I Nr. 2 Chemie-1ng.-Tedln. 25. Jahrg. 1953 I Nr. 2
Introduction: Renal denervation has been shown to be effective in patients with hypertension. Recently, we found that afferent renal neurons show a distinctive feature, exhibiting predominantly a sustained firing upon current injection due to a specific expression of TTX resistant Na-channels. So far, the activity of these specific sensory neurons in hypertension is unclear. Hence we wanted to test the hypothesis that the firing pattern of renal afferent neurons is altered in the 2K/1C model of hypertension. Methods: Hypertension was induced by unilateral clipping of the renal artery in Sprague Dawley rats 3 weeks prior to experiments. Blood pressure was confirmed by an intraarterial measurement. Retrograde labelling (DiI) allowed the identification of renal afferent neurons in the Dorsal root ganglion (DRG Th11-L2). Current clamp was used to characterize neurons as “tonic”, i.e. sustained action potential (AP) firing or “phasic”, i.e. <5 APs according to their firing upon current injections. Electrophysiological parameters and AP properties were determined in neurons of hypertensive animals and controls. Renal morphology was investigated. Results: Renal DRG neurons of hypertensive animals (n=88) showed a significant decrease in tonic firing pattern compared to controls (n=84) (44.3% [39/88] vs. 59.5% [50/84], p< 0.05). Current Clamp analysis revealed no significant change in action potential shape in hypertensive animals (overshoot, firing threshold, AP- duration). Tonic cells revealed a higher capacity in hypertensive rats (124pF vs. 87.8pF, p<0.01), all other parameters (resting potential, resistances) were equal in both groups. No differences in renal pathomorphology could be observed between clipped and non-clipped kidney in hypertensive animals. (BP: 187.5 mmHg versus controls: 106.5mmHg) Conclusion: Hence the excitability of afferent renal neurons in a model of renovascular hypertension is significantly altered, as renal afferent DRG neurons exhibit less sustained firing upon stimulation. Sustained high blood pressure is possibly rather characterized by a generally decreased afferent renal activity with impaired sympathoinhibition than by activated sympathoexcitatory fibers from the clipped kidney.
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