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Abstract: PO2137

Substance P: Differential Influences on Action Potential Production in Afferent Neurons of the Kidney?

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
  • Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
  • Ott, Christian, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
  • Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
  • Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
  • Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
  • Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bavaria, Germany
Background

Afferent nerve fibers of the kidney play a role in controlling sympathetic activity in hypertension and cardiovascular diseases. Proinflammatory substances influence the action potential production of these neurons. Therefore, we tested the hypothesis that proinflammatory substance P (SP) released from afferent nerves inhibits the action potential production in neurons with renal afferents.

Methods

Cultured dorsal root ganglion neurons (DRG Th11-L2) of rats with renal afferents were investigated in current clamp mode to assess action potential generation during both current injections and TRRPV1 stimulation with protons (pH 6) with and without exposure to SP (0.5 µmol) or CGRP (0.5 µmol). Neuronal classification as tonic (high AP generation upon stimulation) and phasic (AP ≤ 5 upon stimulation). Additional experiments were performed in voltage clamp mode to fully assess electrophysiological properties of the neurons.

Results

Renal neurons were stimulated with current injection (14,4+/-1,5 APs/600ms, mean+/- SEM) and protons (9,6+/-1,9 APs/10s of stimulation with pH6). The co-stimulation of renal neurons with current injections and SP decreased the number of action potentials in tonic neurons (15,2+/-1,1 APs/600ms vs. 10,1+/-1,6 APs/600ms, p<0.05, mean+/- SEM), however superfusion of renal neurons with both protons (pH 6) and SP increased it (9,6+/-1,9 APs/10s vs. 16,9+/-2,3 APs/10s, p<0.05, mean+/- SEM). Addition of SP itself did not stimulate cultivated neurons. Co-stimulation with CGRP was without significant effect under any circumstances.

Conclusion

Neuronal SP influences action potential production in renal neurons in a very complex way: Both inhibition and specific increases in action potentials via a TRPV1-dependent mechanism in acid-sensitive renal neurons could be demonstrated. Afferent nerve fibers are likely to respond very specific in different conditions while influencing sympathetic nerve activity and putatively renal physiology or pathology (proinflammatory actions of SP) .

Funding

  • Government Support - Non-U.S.