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¹ Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK
² Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA

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.

(Received 17 May 2007; accepted after revision 3 July 2007; first published online 12 July 2007)
Corresponding author W. Marcotti: Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK. Email: w.marcotti{at}sheffield.ac.uk

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