Journal article

Publication year: 2009

Pages: 40-49

Journal: European Journal of Pharmacology

Volume number: 615

Issue number: 1-3

ISSN: 0014-2999

eISSN: 1879-0712

DOI Link: https://doi.org/10.1016/j.ejphar.2009.04.066

Publisher: Elsevier

Abstract: 

Oxidants, produced e.g. during inflammation, alter gastrointestinal functions finally leading to diarrhoea and/or tissue damage. There is only scarce information about the action of oxidants on enteric neurones, which play a central role in the regulation of many gastrointestinal processes. Therefore, the effect of an oxidant, H2O2, on cultured rat myenteric neurones was studied with the whole-cell patch-clamp and imaging (fura-2) techniques. H2O2 (5 mmol/l) induced an increase in the cytosolic Ca2+ concentration. Both an intracellular release via IP3 and ryanodine receptors as well as a Gd3+-sensitive Ca2+ influx contributed to this response. Measurement of the membrane potential revealed that the neuronal membrane hyperpolarized by 11.3 +/- 0.8 mV in the presence of H2O2. Inhibition of Ca2+-dependent K+ channels prevented this hyperpolarization. Voltage-clamp experiments revealed a second action of the oxidant, i.e. a strong inhibition of the fast Na+ current responsible for the generation of action potentials. This effect seemed to be mediated by the hydroxyl radical ((OH)-O-center dot), as Fe2+ (100 mu mol/l), which leads to the generation of this radical from H2O2 via the Fenton reaction, strongly potentiated the action of an ineffective concentration (100 mu mol/l) of the oxidant. Protein phosphorylation/dephosphorylation seems to be involved in the mechanism of action of H2O2, as the protein phosphatase inhibitor calyculin A (100 nmol/l) strongly reduced the inhibition of Na+ current by H2O2. This effect was mimicked by the protein phosphatase 2A specific inhibitor endothall (100 nmol/l), whereas the PP1 blocker tautomycin (3 nmol/l) was less effective. These results suggest that H2O2 reduces the excitability of rat myenteric neurones by a change of basal membrane potential and an inhibition of Na+ currents.

Harvard Citation style: Pouokam, E., Rehn, M. and Diener, M. (2009) Effects of H2O2 at rat myenteric neurones in culture, European Journal of Pharmacology, 615(1-3), pp. 40-49. https://doi.org/10.1016/j.ejphar.2009.04.066

APA Citation style: Pouokam, E., Rehn, M., & Diener, M. (2009). Effects of H2O2 at rat myenteric neurones in culture. European Journal of Pharmacology. 615(1-3), 40-49. https://doi.org/10.1016/j.ejphar.2009.04.066