Kidney Week

Abstract: FR-PO322

Neurogenic SP Facilitates Action Potential Production in Tonic Highly Sensitive Cultured Neurons with Renal Afferents

Session Information

• Hypertension and CVD: Mechanisms - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Rodionova, Kristina, Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Kristina Rodionova,

• Ditting, Tilmann, Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Tilmann Ditting,

• Schätzl, Johannes, Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Johannes Schätzl,

• Hindermann, Martin, Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Martin Hindermann,

• Ott, Christian, Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Christian Ott,

• Schmieder, Roland E., Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Roland E. Schmieder,

• Amann, Kerstin U., Univestiy of Erlangen-Nuremberg, Erlangen, Germany

Kerstin U. Amann,

• Veelken, Roland, Dept. of Nephrology, Friedrich-Alexander-University Erlangen Nürnberg, Erlangen, Germany

Roland Veelken,

Background

Release of the proinflammatory peptide SP from afferent nerves has been shown to influence local inflammation. But SP is also involved in a powerful sympathoinhibitory afferent renal nerve pathway with a long time-constant. Hence we wanted to test the hypothesis that SP also influences action potential production related to TRPV1 receptor stimulation in cultured neurons with afferent axons from the kidney in vivo.

Methods

Cultured dorsal root ganglion neurons (Th11-L2) of rats with renal afferents in vivo were investigated in current clamp mode to asses action potential (AP) generation and classify neurons as tonic (high AP generation upon stimulation) and phasic (AP < 5 upon stimulation). Furthermore experiments in voltage clamp mode to assess inward currents. For stimulation of TRPV1 receptors acid of pH 6 was used with and without the addition of SP (0.5 µmol) or CGRP (0.5 µmol).

Results

More than 92 DRG neurons with renal afferents were tested. Addition of SP did not change action potential generation nor inward currents. Proton stimulation (pH 6) of TRPV1 significantly increased action potential production in tonic neurons (0 APs/10s vs. 9.57+/-1.89 APs/10s, p<0.05, mean+/- SEM) and augmented long-term inward currents (baseline -361.7 +/- 89.6 pA vs. -1393.3+/-337.3 pA, p<0.05, mean +/- SEM). The co-stimulation of renal neurons with protons (pH 6) and SP increased the number of action potentials per 10 seconds in tonic neurons (9.57 +/-1.89 APs/10s vs. 16.86+/2.3 APs/10s, p<0.05, mean+/- SEM) as compared to a co-stimulation with CGRP, that was not effective in this respect (13.19+/-1,62 APs/10s vs. 9.57 +/-1.89 APs/10s).

Conclusion

SP in contrast to CGRP facilitated action potential production in tonic, highly active neurons with axons from the kidney (a characteristic feature of renal innervation). Hence, SP might increase the sensitivity of afferent renal nerve pathways thus influencing renal sympathetic nerve control.

Funding

• Government Support - Non-U.S.