We have developed a high-throughput patch-clamp screen to identify novel activators of BK channels. We have an assay in cerebellar slices from genetically precise models of ataxia to determine whether agents improve aberrant physiology. We are using in vivo drug delivery to determine whether agents can improve motor dysfunction in mouse models of ataxia. We plan to collaborate with others to further develop the backbone chemistry of promising lead compounds that we have identified, for therapeutic application.