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Genetic deletion of SK2 channels in mouse inner hair cells prevents the developmental linearization in the Ca 2+ dependence of exocytosis
Author(s) -
Johnson Stuart L.,
Adelman John P.,
Marcotti Walter
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.136630
Subject(s) - exocytosis , cochlea , neuroscience , biology , hair cell , electrophysiology , inner ear , mutant , patch clamp , neurotransmitter , ion channel , microbiology and biotechnology , biophysics , chemistry , receptor , endocrinology , biochemistry , central nervous system , gene , secretion
Inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea, fire spontaneous Ca 2+ 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 Ca 2+ ‐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 Ca 2+ channels. Exocytosis was also impaired in adult mutant IHCs, although in this case it resulted from a reduced Ca 2+ efficiency and increased Ca 2+ 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 Ca 2+ dependence of exocytosis in adult IHCs is likely to be a consequence of their disrupted AP activity at immature stages.