Effects of the gaseous signalling molecule nitroxyl (HNO) on myenteric neurons governing intestinal motility

Ervice Pouokam

doi:10.1515/jbcpp-2022-0233

Article

Effects of the gaseous signalling molecule nitroxyl (HNO) on myenteric neurons governing intestinal motility

Ervice Pouokam

Published/Copyright: December 2, 2022

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 34 Issue 5

Abstract

Objectives

The main function of myenteric neurons is the control of gut motility. As we recently showed that nitroxyl (HNO) induces intestinal smooth muscle relaxation, it was of interest to evaluate the effects of this signalling molecule on myenteric neurons in order to distinguish its properties in regard to myocytes.

Methods

Myenteric neurons isolated from the ileum of 4–10 days old rats were used. HNO-induced changes in intracellular concentration of Ca²⁺ or membrane potential and ion currents were measured using the Ca²⁺-sensitive fluorescent dye fura-2 AM or by electrophysiological whole-cell recordings, respectively. Changes in intracellular thiol groups pool were evaluated using thiol tracker violet. Angeli’s salt was used as HNO donor.

Results

The HNO donor Angeli’s salt induced a significant increase in the cytosolic Ca²⁺ concentration at the concentration 50 µM and a membrane hyperpolarization from a resting membrane potential of −56.1 ± 8.0 mV to −63.1 ± 8.7 mV (n=7). Although potassium channels primarily drive membrane potential changes in these cells, outwardly rectifying potassium currents were not significantly affected by 50 µM Angeli’s salt. Fast inward sodium currents were slightly but not significantly reduced by HNO. In more sensitive cells, HNO tended to reduce the pool of thiol groups.

Conclusions

As in the case of smooth muscle cells, HNO causes hyperpolarization of myenteric neurons, an effect also associated with an increase in intracellular Ca²⁺ concentration. Pathways other than activation of potassium currents appear to drive the hyperpolarization evoked by HNO.

Keywords: gaseous signalling molecule; myenteric neurons; nitroxyl

Corresponding author: Ervice Pouokam, PhD, Department of Human medicine, MSB Medical School Berlin, Rüdesheimer Strasse 50, 14197 Berlin, Germany; and Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany, E-mail: ervice.pouokamkamgne@medicalschool-berlin.de

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: PO 2143/1-1

Research funding: This study was supported by a research fund from the German Research Foundation (PO 2143/1-1).
Author contributions: The author has accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2022-08-29

Accepted: 2022-11-14

Published Online: 2022-12-02

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2022-0233

Keywords for this article

gaseous signalling molecule; myenteric neurons; nitroxyl