Overexpression of SK2 channels enhances efferent suppression of cochlear responses without enhancing noise resistance.
Cochlear hair cells express SK2, a small-conductance Ca(2+)-activated K(+) channel thought to act in concert with Ca(2+)-permeable nicotinic acetylcholine receptors (nAChRs) alpha9 and alpha10 in mediating suppressive effects of the olivocochlear efferent innervation. To probe the in vivo role of SK2 channels in hearing, we examined gene expression, cochlear function, efferent suppression, and noise vulnerability in mice overexpressing SK2 channels. Cochlear thresholds, as measured by auditory brain stem responses and otoacoustic emissions, were normal in overexpressers as was overall cochlear morphology and the size, number, and distribution of efferent terminals on outer hair cells. Cochlear expression levels of SK2 channels were elevated eightfold without striking changes in other SK channels or in the alpha9/alpha10 nAChRs. Shock-evoked efferent suppression of cochlear responses was significantly enhanced in overexpresser mice as seen previously in alpha9 overexpresser mice; however, in contrast to alpha9 overexpressers, SK2 overexpressers were not protected from acoustic injury. Results suggest that efferent-mediated cochlear protection is mediated by other downstream effects of ACh-mediated Ca(2+) entry different from those involving SK2-mediated hyperpolarization and the associated reduction in outer hair cell electromotility.
Maison
Stéphane F
SF
Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114-3096, USA. sfm@epl.meei.harvard.edu
Parker
Lisan L
LL
Young
Lucy
L
Adelman
John P
JP
Zuo
Jian
J
Liberman
M Charles
MC
D000818:Animals; D001369:Axons / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D003051:Cochlea / Q000033:anatomy & histology / Q000294:innervation / Q000502:physiology*; D017931:DNA Primers; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009476:Neurons, Efferent / Q000502:physiology*; D009622:Noise / Q000009:adverse effects; D009847:Olivary Nucleus / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis* / Q000235:genetics
D015220:Calcium Channels; D017931:DNA Primers; C496898:Kcnn2 protein, mouse; D051640:Small-Conductance Calcium-Activated Potassium Channels