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Publication : Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits.

First Author  Pyott SJ Year  2007
Journal  J Biol Chem Volume  282
Issue  5 Pages  3312-24
PubMed ID  17135251 Mgi Jnum  J:117811
Mgi Id  MGI:3697763 Doi  10.1074/jbc.M608726200
Citation  Pyott SJ, et al. (2007) Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits. J Biol Chem 282(5):3312-24
abstractText  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 alpha and beta subunits in mammalian inner hair cells, we analyzed the morphology, physiology, and function of these cells from mice lacking the BK channel alpha (Slo-/-) and also the beta1 and beta4 subunits (beta1/4-/-). Beta1/4-/- mice showed normal subcellular localization, developmental acquisition, and expression of BK channels. Beta1/4-/- 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 BKalpha 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.
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