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

Sci Rep. 2017 Feb 14:7:42433. doi: 10.1038/srep42433.


Large 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain Stem / physiology
  • Cell Line
  • Evoked Potentials, Auditory
  • Humans
  • Inferior Colliculi / drug effects*
  • Inferior Colliculi / metabolism*
  • Ion Channel Gating
  • Large-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors*
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Mesencephalon / physiology
  • Mice
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Potassium Channel Blockers / chemistry
  • Potassium Channel Blockers / pharmacology*


  • Large-Conductance Calcium-Activated Potassium Channels
  • Peptides
  • Potassium Channel Blockers