title: Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1.
abstract: 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 patch-clamp recording. The firing pattern of neurons was characterized as tonic, i.e., sustained action potential (AP) firing, or phasic, i.e., <5 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 < 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 < 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 < 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.
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Tilmann
authors.initials: T
authors.lastname: Ditting
authors.affiliation: Department of Internal Medicine 1, Nephrology Johannes-Guttenberg University, Mainz, Germany;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Freisinger
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Kristina
authors.initials: K
authors.lastname: Rodionova
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Schatz
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Nena
authors.initials: N
authors.lastname: Lale
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Sonja
authors.initials: S
authors.lastname: Heinlein
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Linz
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany;
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
authors.affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago Stritch School of Medicine, Chicago, Illinois.
authors.forename: Karie E
authors.initials: KE
authors.lastname: Scrogin
authors.affiliation: Department of Internal Medicine 4, Nephrology and Hypertension, Friedrich-Alexander University, Erlangen, Germany; roland.veelken@uk-erlangen.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Veelken
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D007668:Kidney / Q000294:innervation*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley
chemical_list: D054360:Chemokine CXCL1
keywords: CXCL1; chemokine; firing pattern; phasic; renal afferent nerve; tonic; voltage-gated sodium channel