Abstract: SA-PO784
Afferent Neurons of the Kidney With Impaired Firing Pattern in Inflammation: Role of Sodium and Potassium Currents
Session Information
- Hypertension and CVD: Mechanisms
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1503 Hypertension and CVD: Mechanisms
Authors
- Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Linz, Peter, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Ott, Christian, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
- Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany
Background
Previously, we reported that peripheral neurons with renal afferents involved in sympathetic control exhibit a predominantly tonic firing pattern of higher frequency that is reduced to low frequencies (phasic firing pattern) in renal inflammation (and hypertension). Now, we wanted to test the hypothesis that the reduction in firing activity during inflammation is due to special tonic neurons switching from higher to low frequencies.
Methods
Renal subcapsular staining (DiI) for identification of neurons with renal projection (RANs). Cultivated neurons incubated with the chemokine CXCL1 (1,5 nmol/ml) for 12 hours prior to electrophysiology. Current clamp used to characterize neurons as “tonic”, i.e. sustained action potential (AP) firing or “phasic”, i.e. <5 APs upon stimulation. Membrane currents investigated by increasing clamp voltage. Data analyzed: renal vs. non-renal and tonic vs. phasic neurons.
Results
Renal neurons exposed to CXCL1 showed a decrease of tonic firing pattern compared to controls (35,6% vs. 57%, P<0.05). Phasic neurons exhibited higher Na+ and K+ currents than tonic neurons in controls resulting in shorter APs (3.7±0,3 vs. 6.1±0,6 ms, P<0,01). In neurons incubated with CXCL1, Na+ and K+ peak currents increased (Na+: -969±47 vs. -758±47 nA/pF, P<0.01; K+: 707±22 vs. 558±31 nA/pF, P<0.01) in phasic, but were unchanged in tonic neurons. Incubated phasic neurons showed a much broader range of Na+ currents ([-365 – -1429 nA] vs. [-412 – -4273 nA]; P<0.05); similar to tonic neurons.
Conclusion
The enlarged number of renal phasic neurons incubated with CXCL1 showed significantly increased membrane currents ressembling the broad range of Na+ currents seen in tonic neurons. These findings suggest that a subgroup of tonic neurons switched to a phasic response pattern in inflammation while other mechanisms become less likely (e.g. recruitment of formerly silent phasic neurons).
Funding
- Government Support – Non-U.S.