title: Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea.
abstract: Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined action of ionotropic acetylcholine receptors and associated calcium-activated potassium channels. Although inhibition was thought to involve exclusively small conductance (SK potassium channels), recent findings have shown that BK channels also contribute to inhibition in basal, high-frequency OHCs after the onset of hearing. Here we show that the waveform of randomly timed IPSCs (evoked by high extracellular potassium) in high-frequency OHCs is altered by blockade of either SK or BK channels, with BK channels supporting faster synaptic waveforms and SK channels supporting slower synaptic waveforms. Consistent with these findings, IPSCs recorded from high-frequency OHCs that express BK channels are briefer than IPSCs recorded from low-frequency (apical) OHCs that do not express BK channels and from immature high-frequency OHCs before the developmental onset of BK channel expression. Likewise, OHCs of BKα(-/-) mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα(+/+) littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα(-/-) OHCs were smaller than those of BKα(+/+) OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα(-/-) OHCs were smaller than those of BKα(+/+) OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.
authors: Department of Otolaryngology Head and Neck Surgery, Center for Hearing and Balance, and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 and.
authors: Kevin N
authors: http://orcid.org/0000-0003-3565-8489
authors: KN
authors: Rohmann
authors: Department of Otolaryngology Head and Neck Surgery, Center for Hearing and Balance, and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 and.
authors: Eric
authors: E
authors: Wersinger
authors: Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina 28403.
authors: Jeremy P
authors: JP
authors: Braude
authors: Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina 28403.
authors: Sonja J
authors: SJ
authors: Pyott
authors: Department of Otolaryngology Head and Neck Surgery, Center for Hearing and Balance, and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 and pfuchs1@jhmi.edu.
authors: Paul Albert
authors: http://orcid.org/0000-0003-4627-4114
authors: PA
authors: Fuchs
mesh_terms: D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism / Q000502:physiology; D005260:Female; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism* / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009476:Neurons, Efferent / Q000378:metabolism / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D051640:Small-Conductance Calcium-Activated Potassium Channels
keywords: BK channel; SK channel; cholinergic inhibition; cochlea; efferent inhibition; outer hair cell
references: Neuron. 2000 Jun;26(3):595-601
references: 10896156
references: J Neurosci. 2014 Dec 10;34(50):16688-97
references: 25505321
references: J Biol Chem. 2004 Aug 27;279(35):36746-52
references: 15184377
references: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12922-7
references: 15328414
references: J Neurosci. 2004 Sep 8;24(36):7814-20
references: 15356192
references: J Neurosci. 2004 Oct 27;24(43):9469-74
references: 15509733
references: Naturwissenschaften. 1974 Nov;61(11):506-7
references: 4449570
references: J Comp Physiol Psychol. 1977 Aug;91(4):930-6
references: 893752
references: Proc Biol Sci. 1990 Aug 22;241(1301):122-6
references: 1978338
references: Hear Res. 1991 Feb;51(2):247-54
references: 2032960
references: Proc Biol Sci. 1991 May 22;244(1310):161-7
references: 1679550
references: J Neurosci. 1992 Jan;12(1):297-305
references: 1370323
references: J Neurosci. 1992 Mar;12(3):800-9
references: 1545240
references: J Physiol. 1991 Oct;442:669-90
references: 1798048
references: Cell. 1994 Nov 18;79(4):705-15
references: 7954834
references: J Physiol. 1996 Mar 1;491 ( Pt 2):563-78
references: 8866879
references: J Physiol. 1996 Nov 1;496 ( Pt 3):639-46
references: 8930832
references: J Neurosci. 1997 Jan 1;17(1):428-37
references: 8987768
references: Annu Rev Physiol. 1999;61:809-34
references: 10099711
references: J Neurosci. 2004 Dec 8;24(49):11160-4
references: 15590932
references: Neuroscience. 2005;130(2):475-84
references: 15664704
references: Hear Res. 2005 Apr;202(1-2):63-73
references: 15811700
references: J Microsc. 2005 Apr;218(Pt 1):52-61
references: 15817063
references: Curr Opin Neurobiol. 2005 Jun;15(3):305-11
references: 15922588
references: J Physiol. 2005 Jul 1;566(Pt 1):103-18
references: 15860528
references: Hear Res. 2005 Nov;209(1-2):1-9
references: 16005587
references: J Neurosci. 2006 Oct 25;26(43):10992-1000
references: 17065441
references: Neuroscience. 2006 Dec13;143(3):837-49
references: 17074442
references: Brain Res. 2007 Jan 19;1129(1):110-5
references: 17157279
references: J Biol Chem. 2007 Feb 2;282(5):3312-24
references: 17135251
references: Neuron. 2008 Sep 25;59(6):873-81
references: 18817728
references: Mol Neurobiol. 2008 Oct;38(2):153-66
references: 18759010
references: J Physiol. 2008 Nov 15;586(22):5471-85
references: 18818242
references: Mol Cell Neurosci. 2009 Jan;40(1):39-49
references: 18848895
references: Biochem Pharmacol. 2009 Oct 1;78(7):712-9
references: 19481062
references: Trends Neurosci. 2010 Sep;33(9):415-23
references: 20663573
references: J Neurosci. 2010 Sep 8;30(36):12157-67
references: 20826678
references: Physiol Rev. 2010 Oct;90(4):1437-59
references: 20959620
references: PLoS One. 2010;5(11):e13836
references: 21079807
references: Neuron. 2011 Jun 23;70(6):1143-54
references: 21689600
references: Hear Res. 2011 Sep;279(1-2):1-12
references: 21187136
references: J Neurosci. 2011 Oct 12;31(41):14763-74
references: 21994392
references: J Neurosci. 2011 Oct 19;31(42):15092-101
references: 22016543
references: FASEB J. 2012 Sep;26(9):3834-43
references: 22691916
references: J Neurophysiol. 2013 Mar;109(6):1525-34
references: 23282326
references: J Comp Neurol. 2014 Feb 15;522(3):717-29
references: 24122766
references: Channels (Austin). 2014;8(1):62-75
references: 24394769
references: Science. 2000 Jun 30;288(5475):2366-8
references: 10875922
references: J Comp Physiol A. 1999 Nov;185(5):455-62
references: 10573868
references: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3501-6
references: 11248107