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Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC<jats:sub>50<\/jats:sub> in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins. LS3 suppresses locomotor activity via a BK channel-specific mechanism in wild-type or BK channel-humanized <jats:italic>Caenorhabditis elegans<\/jats:italic>. Topical application on the dural surface of the auditory midbrain in mouse suppresses sound evoked neural activity, similar to a well-characterized pore blocker of the BK channel. Moreover, this novel ion channel-targeted peptide rapidly crosses the BBB after systemic delivery to modulate auditory processing. Thus, a potent BK channel peptide modulator is open to neurological applications, such as preventing audiogenic seizures that originate in the auditory midbrain.<\/jats:p>","DOI":"10.1038\/srep42433","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T12:53:52Z","timestamp":1487076832000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus"],"prefix":"10.1038","volume":"7","author":[{"given":"L. L.","family":"Scott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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