Cochlear function in mice lacking the BK channel α, β1, or β4 subunits

Sonja J. Pyott, Andrea L. Meredith, Anthony A. Fodor, Ana E. Vázquez, Ebenezer N. Yamoah, Richard W. Aldrich

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Large conductance voltage- and calcium-activated potassium (BK) channels are important for regulating many essential cellular functions, from neuronal action potential shape and firing rate to smooth muscle contractility. In amphibians, reptiles, and birds, BK channels mediate the intrinsic frequency tuning of the cochlear hair cell by an electrical resonance mechanism. In contrast, inner hair cells of the mammalian cochlea are extrinsically tuned by accessory structures of the cochlea. Nevertheless, BK channels are present in inner hair cells and encode a fast activating outward current. To understand the role of the BK channel α and β subunits in mammalian inner hair cells, we analyzed the morphology, physiology, and function of these cells from mice lacking the BK channel α(Slo-/-) and also the β1 and β4 subunits (β1/4-/-). β1/4-/- mice showed normal subcellular localization, developmental acquisition, and expression of BK channels. β1/4-/- mice showed normal cochlear function as indicated by normal auditory brainstem responses and distortion product otoacoustic emissions. Slo-/- mice also showed normal cochlear function despite the absence of the BKα subunit and the absence of fast activating outward current from the inner hair cells. Moreover, microarray analyses revealed no compensatory changes in transcripts encoding ion channels or transporters in the cochlea from Slo-/- mice. Slo-/- mice did, however, show increased resistance to noise-induced hearing loss. These findings reveal the fundamentally different contribution of BK channels to nonmammalian and mammalian hearing and suggest that BK channels should be considered a target in the prevention of noise-induced hearing loss.

Original languageEnglish (US)
Pages (from-to)3312-3324
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number5
DOIs
StatePublished - Jan 2 2007

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Cochlear function in mice lacking the BK channel α, β1, or β4 subunits'. Together they form a unique fingerprint.

  • Cite this

    Pyott, S. J., Meredith, A. L., Fodor, A. A., Vázquez, A. E., Yamoah, E. N., & Aldrich, R. W. (2007). Cochlear function in mice lacking the BK channel α, β1, or β4 subunits. Journal of Biological Chemistry, 282(5), 3312-3324. https://doi.org/10.1074/jbc.M608726200