A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus

• DOI: 10.1038/srep42433
• Publication Date: 2017-02-14T12:53:52Z
• Authors: L. L. Scott; E. J. Brecht; A. Philpo; S. Iyer; N. S. Wu; S. J. Mihic; R. W. Aldrich; J. Pierce; J. P. Walton
• Keywords: Inferior Colliculi

Abstract Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest pharmaceutical applications for modulating BK channel function. Here we report a novel channel-targeted peptide with functional activity vitro vivo . This 9-amino acid peptide, LS3, has unique action, suppressing gating rather than blocking the pore heterologously human channels. With IC 50 high picomolar range, apparent affinity is higher known toxins. LS3 suppresses locomotor via channel-specific mechanism wild-type or channel-humanized Caenorhabditis elegans Topical application on dural surface auditory midbrain mouse sound evoked neural activity, similar to well-characterized blocker channel. Moreover, this ion rapidly crosses BBB after systemic delivery processing. Thus, potent modulator open neurological applications, such as preventing audiogenic seizures that originate midbrain.