Kidney Week

Abstract: TH-PO0293

Nav1.8 Sodium Channels Are Necessary for High Active Afferent Neurons in Renal Afferent Nerve Fibers

Session Information

• Hypertension and CVD: Mechanisms
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Hutter, Eva, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Eva Hutter, MSc

• Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Tilmann Ditting, MD

• Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Karl F. Hilgers, MD, FASN

• Linz, Peter, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Peter Linz, PhD

• Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Roland E. Schmieder, MD, FASN

• Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Mario Schiffer, MD, DrMed, MBA

• Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Kerstin U. Amann, MD

• Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Roland Veelken, MD, DrMed

• Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Kristina Rodionova, MD

Background

Our previous results suggested that afferent renal nerve fibers with neurons in the dorsal root ganglia (DRG Th12-L2) induce significant sympathoinhibition lost during inflammation with oxidative stress as in nephritis and hypertension. High afferent nerve activity depends likely on neuronal Nav1.8 sodium channels. To put this assumption on a broader basis, we tested the following hypothesis: Native renal DRG neurons as well as immortalized DRG neurons with known expression of Nav 1.8 (F11) show in contrast to immortalized DRG neurons with scarce Nav 1.8 expression (ND7/23) highly active response patterns to electrical stimulation reduced by an oxidant.

Methods

Immortalized DRG lines F11 and ND7/23 were differentiated in cell medium with neural growth factor (NGF) for 5-10 days, native DRG neurons with renal afferents in vivo were freshly used after harvesting. In all neuronal cultures, action potential generation (AP) was assessed during current injection to characterize neurons as tonic highly active (> 5 AP) and phasic less active ones. In addition, the F11 cells were perfused with Chloramine T (10µM Chloramine T,150 s).

Results

Immortalized DRG lines F11 and ND7/23 were differentiated in cell medium with neural growth factor (NGF) for 5-10 days, native DRG neurons with renal afferents in vivo were freshly used after harvesting. In all neuronal cultures, action potential generation (AP) was assessed during current injection to characterize neurons as tonic highly active (> 5 AP) and phasic less active ones. In addition, the F11 cells were perfused with Chloramine T (10µM Chloramine T,150 s).

F11 cells with known Na_v1.8 expression showed a significantly higher proportion of tonic highly active neurons (41%) than ND7/23 cells (6% tonic). The portion of tonic F11 neurons was comparable to the one in native renal DRG samples. After perfusion with proinflammatory oxidant chloramine T, tonic F11 neurons like native neurons produced significantly fewer action potentials.

Conclusion

Expression of Na_v1.8 sodium channels in DGR neurons of various origin (immortalized, renal native) were necessary for tonic high frequency AP production. This response was weakened by an oxidant like Chloramine T suggesting that afferent renal nerve function is impaired by oxidative stress.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202557tp7vm6