title: Olivocochlear suppression of outer hair cells in vivo: evidence for combined action of BK and SK2 channels throughout the cochlea.
abstract: Cholinergic inhibition of cochlear hair cells via olivocochlear (OC)-efferent feedback is mediated by Ca(2+) entry through α9-/α10-nicotinic receptors, but the nature of the K(+) channels activated by this Ca(2+) entry has been debated (Yoshida N, Hequembourg SJ, Atencio CA, Rosowski JJ, Liberman MC. J Neurophysiol 85: 84-88, 2001). A recent in vitro study (Wersinger E, McLean WJ, Fuchs PA, Pyott SJ. PLoS One 5: e13836, 2010) suggests that small-conductance (SK2) channels mediate cholinergic effects in the apical turn, whereas large-conductance (BK) channels mediate basal turn effects. Here, we measure, as a function of cochlear frequency, the magnitude of BK and SK2 expression in outer hair cells and the strength of in vivo OC suppression in BK(+/+) mice vs. BK(-/-) lacking the obligatory α-subunit (Meredith AL, Thorneloe KS, Werner ME, Nelson MT, Aldrich RW. J Biol Chem 279: 36746-36752, 2004). Except at the extreme apical tip, we see immunostaining for both BK and SK2 in BK(+/+). Correspondingly, at all testable frequencies (8-45 kHz), we see evidence for both SK2 and BK contributions to OC effects evoked by electrically stimulating the OC bundle: OC-mediated suppression was reduced, but not eliminated, at all frequencies in the BK(-/-) ears. The suppression remaining in BK nulls was blocked by strychnine, suggesting involvement of α9-/α10-cholinergic receptors, coupled to activation of the remaining SK2 channels.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts, USA. stephane_maison@meei.harvard.edu
authors.forename: Stéphane F
authors.initials: SF
authors.lastname: Maison
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Pyott
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Meredith
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003051:Cochlea / Q000166:cytology / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000502:physiology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology
chemical_list: C496898:Kcnn2 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013331:Strychnine