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Ion channels are important molecules for membrane excitability in the nervous system and signal transduction in non-excitable tissues.Applying conventional high throughput technologies and automated electrophysiology, we have screened large compound libraries in the order of more than 300,000 structures for modulators of several classes of ion channels.Detailed characterizations of these active compounds are under way and have begun to reveal both diverse and novel regulatory mechanisms.This information provides new insights into chemical regulation and drug development for ion channels.