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Genetic deletion of SK2 channels in mouse inner hair cells prevents the developmental linearization in the Ca2+ dependence of exocytosis

Johnson, S.L., Adelman, J.P. and Marcotti, W. (2007) Genetic deletion of SK2 channels in mouse inner hair cells prevents the developmental linearization in the Ca2+ dependence of exocytosis. The Journal of Physiology, 583 (2). pp. 631-646. ISSN 0022-3751

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Inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea, fire spontaneous Ca2+ action potentials (APs) only before the onset of hearing. Although a role for APs in the developing auditory system has not been determined it could, by analogy with other sensory systems, guide the functional maturation of the cochlea before experience-driven activity begins. Spontaneous APs in immature IHCs are shaped by a variety of ion channels including that of the small conductance Ca2+-activated K+ current (SK2), which is only transiently expressed in immature cells. Using SK2 knockout mice we found that SK2 channels are not required for generating APs but are essential for sustaining continuous repetitive spontaneous AP activity in pre-hearing IHCs. Therefore we used this mutant mouse as a model to study possible developmental implications of disrupted AP activity. Immature mutant IHCs showed impaired exocytotic responses, which are likely to be due to the expression of fewer Ca2+ channels. Exocytosis was also impaired in adult mutant IHCs, although in this case it resulted from a reduced Ca2+ efficiency and increased Ca2+ dependence of the synaptic machinery. Since SK2 channels can only have a functional influence on IHCs during immature development and are not directly involved in neurotransmitter release, the altered Ca2+ dependence of exocytosis in adult IHCs is likely to be a consequence of their disrupted AP activity at immature stages.

Item Type: Article
Copyright, Publisher and Additional Information: Freely available from the publisher web site.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Ms Suzannah Rockett
Date Deposited: 04 Sep 2008 17:38
Last Modified: 04 Sep 2008 17:38
Published Version: http://dx.doi.org/10.1113/jphysiol.2007.136630
Status: Published
Publisher: Blackwell Publishing
Refereed: Yes
Identification Number: 10.1113/jphysiol.2007.136630
Related URLs:
URI: http://eprints.whiterose.ac.uk/id/eprint/4602

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