title: Transduction without tip links in cochlear hair cells is mediated by ion channels with permeation properties distinct from those of the mechano-electrical transducer channel.
abstract: Tip links between adjacent stereocilia are believed to gate mechano-electrical transducer (MET) channels and mediate the electrical responses of sensory hair cells. We found that mouse auditory hair cells that lack tip links due to genetic mutations or exposure to the Ca(2+) chelator BAPTA can, however, still respond to mechanical stimuli. These MET currents have unusual properties and are predominantly of the opposite polarity relative to those measured when tip links are present. There are other striking differences, for example, the channels are usually all closed when the hair cell is not stimulated and the currents in response to strong stimuli can be substantially larger than normal. These anomalous MET currents can also be elicited early in development, before the onset of mechano-electrical transduction with normal response polarity. Current-voltage curves of the anomalous MET currents are linear and do not show the rectification characteristic of normal MET currents. The permeant MET channel blocker dihydrostreptomycin is two orders of magnitude less effective in blocking the anomalous MET currents. The findings suggest the presence of a large population of MET channels with pore properties that are distinct from those of normal MET channels. These channels are not gated by hair-bundle links and can be activated under a variety of conditions in which normal tip-link-mediated transduction is not operational.
authors.affiliation: Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, United Kingdom, and Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
authors.forename: Laura F
authors.initials: LF
authors.lastname: Corns
authors.forename: Terri
authors.initials: T
authors.lastname: Desmonds
authors.forename: Nerissa K
authors.initials: NK
authors.lastname: Kirkwood
authors.forename: Guy P
authors.initials: GP
authors.lastname: Richardson
authors.forename: Corné J
authors.initials: CJ
authors.lastname: Kros
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics; D002463:Cell Membrane Permeability / Q000235:genetics / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004096:Dihydrostreptomycin Sulfate / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004622:Embryo, Mammalian; D005260:Female; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics; D009925:Organ of Corti / Q000166:cytology; D011498:Protein Precursors / Q000235:genetics
chemical_list: C418976:CDHR15 protein, mouse; D000070585:Cadherin Related Proteins; D015820:Cadherins; C499091:Cdh23 protein, mouse; D002614:Chelating Agents; D007473:Ion Channels; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D011498:Protein Precursors; D004533:Egtazic Acid; D009218:Myosins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D004096:Dihydrostreptomycin Sulfate
keywords: aminoglycoside antibiotics; cochlea; hair cell; mechano-electrical transduction
references.citation: J Physiol. 2003 Mar 15;547(Pt 3):873-91
references.pmid: 12562920
references.citation: J Physiol. 2003 Apr 15;548(Pt 2):383-400
references.pmid: 12588897
references.citation: PLoS One. 2011 Apr 21;6(4):e19183
references.pmid: 21532990
references.citation: Proc Biol Sci. 1997 Apr 22;264(1381):611-21
references.pmid: 9149428
references.citation: J Gen Physiol. 2013 Nov;142(5):481-6
references.pmid: 24127528
references.citation: J Comp Neurol. 2010 Nov 1;518(21):4288-97
references.pmid: 20853507
references.citation: Neuron. 2013 Nov 20;80(4):960-72
references.pmid: 24267652
references.citation: Neuron. 1991 Dec;7(6):985-94
references.pmid: 1764247
references.citation: J Neurophysiol. 2010 Jul;104(1):18-34
references.pmid: 20427623
references.citation: Dev Cell. 2012 Aug 14;23(2):329-41
references.pmid: 22898777
references.citation: J Physiol. 1991 Mar;434:369-98
references.pmid: 1708822
references.citation: Proc Biol Sci. 1992 Aug 22;249(1325):185-93
references.pmid: 1280836
references.citation: Neuron. 2013 Aug 7;79(3):504-15
references.pmid: 23871232
references.citation: J Neurosci. 2006 Oct 25;26(43):10992-1000
references.pmid: 17065441
references.citation: J Neurophysiol. 2009 Jun;101(6):2961-73
references.pmid: 19339464
references.citation: Nature. 2007 Sep 6;449(7158):87-91
references.pmid: 17805295
references.citation: J Physiol. 2005 Sep 1;567(Pt 2):505-21
references.pmid: 15994187
references.citation: J Clin Invest. 2011 Dec;121(12):4796-809
references.pmid: 22105175
references.citation: Hear Res. 1987 Nov;31(1):9-24
references.pmid: 3429352
references.citation: Nat Neurosci. 2003 Aug;6(8):832-6
references.pmid: 12872124
references.citation: J Gen Physiol. 2013 Nov;142(5):493-505
references.pmid: 24127526
references.citation: J Neurosci. 2006 Jun 28;26(26):7022-34
references.pmid: 16807332
references.citation: J Neurophysiol. 2012 May;107(9):2408-20
references.pmid: 22323630
references.citation: Nature. 2004 Apr 29;428(6986):955-9
references.pmid: 15057246
references.citation: Nat Neurosci. 2002 Jan;5(1):41-7
references.pmid: 11753415
references.citation: J Neurosci. 2003 Jun 15;23(12):4878-87
references.pmid: 12832510
references.citation: J Neurosci. 2001 Sep 15;21(18):7013-25
references.pmid: 11549711
references.citation: J Neurosci. 2010 Aug 25;30(34):11259-69
references.pmid: 20739546
references.citation: Nature. 2004 Apr 29;428(6986):950-5
references.pmid: 15057245
references.citation: J Comp Neurol. 2005 Apr 25;485(1):75-85
references.pmid: 15776440
references.citation: J Neurosci. 2007 Dec 12;27(50):13890-902
references.pmid: 18077701
references.citation: J Physiol. 1989 Dec;419:405-34
references.pmid: 2621635
references.citation: J Gen Physiol. 2013 Jan;141(1):141-8
references.pmid: 23277480
references.citation: Neurosci Lett. 1991 Dec 9;133(2):171-4
references.pmid: 1726184
references.citation: Hear Res. 1991 Nov;56(1-2):19-28
references.pmid: 1722801
references.citation: Curr Top Membr. 2007;59:375-98
references.pmid: 25168143
references.citation: Nat Neurosci. 2009 May;12(5):553-8
references.pmid: 19330002
references.citation: J Physiol. 1999 Nov 1;520 Pt 3:653-60
references.pmid: 10545133
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11476-81
references.pmid: 21709241