A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus
0301 basic medicine
Article
Inferior Colliculi
Cell Line
Mice
03 medical and health sciences
Mesencephalon
Evoked Potentials, Auditory
Potassium Channel Blockers
Animals
Humans
Amino Acid Sequence
Large-Conductance Calcium-Activated Potassium Channels
Peptides
Ion Channel Gating
Brain Stem
DOI:
10.1038/srep42433
Publication Date:
2017-02-14T12:53:52Z
AUTHORS (9)
ABSTRACT
AbstractLarge conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. 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 in vitro and in vivo. 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 IC50 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 Caenorhabditis elegans. 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.
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CITATIONS (17)
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