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 gastrointestinal regulation. 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^-1) 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 (n = 30) 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. an 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 Fe²⁺ (100 mmmol ^. l^-1), which leads to the generation of this radical from H₂O₂ via the Fenton reaction, strongly potentiated the action of an ineffective concentration (100 mmmol ^. l^-1) of the oxidant. Protein phosphorylation/dephosphorylation seems to be involved in the mechanism of action of H₂O₂, as the protein phosphatase (PP) inhibitor calyculin A strongly reduced the inhibition of Na⁺ current by H₂O₂. This effect was mimicked by the PP2A specific inhibitor endothall. These results suggest that H₂O₂ reduces the excitability of rat myenteric neurones.