Effects of H2O2 at rat myenteric neurones in culture

Eur J Pharmacol. 2009 Aug 1;615(1-3):40-9. doi: 10.1016/j.ejphar.2009.04.066. Epub 2009 May 14.


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, H(2)O(2), on cultured rat myenteric neurones was studied with the whole-cell patch-clamp and imaging (fura-2) techniques. H(2)O(2) (5 mmol/l) induced an increase in the cytosolic Ca(2+) concentration. Both an intracellular release via IP(3) and ryanodine receptors as well as a Gd(3+)-sensitive Ca(2+) 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 H(2)O(2). Inhibition of Ca(2+)-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), as Fe(2+) (100 micromol/l), which leads to the generation of this radical from H(2)O(2) via the Fenton reaction, strongly potentiated the action of an ineffective concentration (100 micromol/l) of the oxidant. Protein phosphorylation/dephosphorylation seems to be involved in the mechanism of action of H(2)O(2), as the protein phosphatase inhibitor calyculin A (100 nmol/l) strongly reduced the inhibition of Na(+) current by H(2)O(2). 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 H(2)O(2) reduces the excitability of rat myenteric neurones by a change of basal membrane potential and an inhibition of Na(+) currents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology*
  • Intestine, Small / innervation
  • Membrane Potentials
  • Myenteric Plexus / drug effects*
  • Myenteric Plexus / physiology
  • Neurons / drug effects*
  • Neurons / physiology
  • Oxidants / metabolism
  • Oxidants / pharmacology*
  • Patch-Clamp Techniques
  • Phosphorylation
  • Potassium Channels, Calcium-Activated / physiology
  • Rats
  • Ryanodine Receptor Calcium Release Channel / physiology
  • Sodium Channels / physiology


  • Oxidants
  • Potassium Channels, Calcium-Activated
  • Ryanodine Receptor Calcium Release Channel
  • Sodium Channels
  • Hydrogen Peroxide
  • Calcium