title: Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?
abstract: 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 (Navs). Dorsal root ganglion (DRG) neurons from rats (Th11-L2) were recorded by the current-clamp technique and distinguished as "tonic" or "phasic." In voltage-clamp recordings, Navs were characterized by their tetrodotoxoxin (TTX) sensitivity, and their molecular identity was revealed by RT-PCR. The firing pattern of 66 DRG neurons (41 renal and 25 nonrenal) was investigated. Renal neurons exhibited more often a tonic firing pattern (56.1 vs. 12%). Tonic neurons showed a more positive threshold (-21.75 ± 1.43 vs.-29.33 ± 1.63 mV; P < 0.05), a higher overshoot (56.74 [53.6-60.96] vs. 46.79 mV [38.63-54.75]; P < 0.05) and longer action potential duration (4.61 [4.15-5.85] vs. 3.35 ms [2.12-5.67]; P < 0.05). These findings point to an increased presence of the TTX-resistant Navs 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 Navs.
authors.affiliation: Dept. of Medicine 4, Univ. of Erlangen-Nürnberg, Loschgestraβe 8, 91054 Erlangen, Germany. wolfgang.freisinger@uk-erlangen.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Freisinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Schatz
authors.forename: Tilmann
authors.initials: T
authors.lastname: Ditting
authors.forename: Angelika
authors.initials: A
authors.lastname: Lampert
authors.forename: Sonja
authors.initials: S
authors.lastname: Heinlein
authors.forename: Nena
authors.initials: N
authors.lastname: Lale
authors.forename: Roland
authors.initials: R
authors.lastname: Schmieder
authors.forename: Roland
authors.initials: R
authors.lastname: Veelken
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000294:innervation* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D061566:Voltage-Gated Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D061566:Voltage-Gated Sodium Channels