Abstract: Objective To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition. Methods We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K + concentration or the application of an antagonist of GABAA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs. Results Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K + ]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K+]o and disinhibition models. Conclusion ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.

Key words: epilepsy, extracellular acidosis, acid-sensitive ion channels, ASICs, field potential recording