SK2 channels are required for function and long-term survival of efferent synapses on mammalian outer hair cells.
Cochlear hair cells use SK2 currents to shape responses to cholinergic efferent feedback from the brain. Using SK2(-/-) mice, we demonstrate that, in addition to their previously defined role in modulating hair cell membrane potentials, SK2 channels are necessary for long-term survival of olivocochlear fibers and synapses. Loss of the SK2 gene also results in loss of electrically driven olivocochlear effects in vivo, and down regulation of ryanodine receptors involved in calcium-induced calcium release, the main inducer of nAChR evoked SK2 activity. Generation of double-null mice lacking both the alpha10 nAChR gene, loss of which results in hypertrophied olivocochlear terminals, and the SK2 gene, recapitulates the SK2(-/-) synaptic phenotype and gene expression, and also leads to down regulation of alpha9 nAChR gene expression. The data suggest a hierarchy of activity necessary to maintain early olivocochlear synapses at their targets, with SK2 serving an epistatic, upstream, role to the nAChRs.
Dept. of Neuroscience, Tufts Univ. School of Medicine, 136 Harrison Ave. Boston, MA 02111, USA.
Vidya
V
Murthy
Stéphane F
SF
Maison
Julián
J
Taranda
Nadeem
N
Haque
Chris T
CT
Bond
A Belén
AB
Elgoyhen
John P
JP
Adelman
M Charles
MC
Liberman
Douglas E
DE
Vetter
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D003051:Cochlea / Q000166:cytology* / Q000294:innervation* / Q000502:physiology; D004525:Efferent Pathways / Q000033:anatomy & histology* / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009847:Olivary Nucleus / Q000033:anatomy & histology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
C526014:Chrna10 protein, mouse; C402445:Chrna9 protein, mouse; C496898:Kcnn2 protein, mouse; D019006:Neural Cell Adhesion Molecules; D011978:Receptors, Nicotinic; D051640:Small-Conductance Calcium-Activated Potassium Channels; D016708:Synaptophysin