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Abstract. K + channels are key modulators of neuronal excitability, and mutations in certain types of these channels are known to cause epileptic seizures. Activation of K + channels is reported to suppress epileptic discharge; however, the types of K + -channel openers that are most effective as anti-epileptic agents are not well understood. We established a quantitative fluorescence assay using the Na + indicator sodium-binding benzofuran isophthalate (SBFI) for evaluation of various compounds on epileptiform activities induced by 4-aminopyridine (4-AP) in cultured rat hippocampal neurons. Among the K + -channel openers, the K V 7.2 / K V 7.3-channel openers retigabine and flupirtine and K Ca 2-channel openers NS309, DCEBIO, and 1-EBIO showed potent anti-epileptic effects similar to conventional antiepileptic drugs (AEDs). In contrast, the K Ca 1.1-channel openers NS1619, isopimaric acid, and chlorzoxazone demonstrated moderate inhibition. The K ir 6-channel openers minoxidil, cromakalim, and pinacidil did not show anti-epileptic effects. We concluded that K V 7.2 / K V 7.3, K Ca 2, and, to some extent, K Ca 1.1-channel openers, but not K ir 6-channel openers, suppress 4-AP-induced epileptiform activities in hippocampal neurons. These results suggest that the K + -channel openers for this category of K + channels might have therapeutic potential as new classes of antiepileptic drugs.

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