title: Developmental alterations in the biophysical properties of Ca(v) 1.3 Ca(2+) channels in mouse inner hair cells.
abstract: Prior to hearing onset, spontaneous action potentials activate voltage-gated Cav 1.3 Ca ( 2+) channels in mouse inner hair cells (IHCs), which triggers exocytosis of glutamate and excitation of afferent neurons. In mature IHCs, Cav 1.3 channels open in response to evoked receptor potentials, causing graded changes in exocytosis required for accurate sound transmission. Developmental alterations in Cav 1.3 properties may support distinct roles of Cav 1.3 in IHCs in immature and mature IHCs, and have been reported in various species. It is not known whether such changes in Cav 1.3 properties occur in mouse IHCs, but this knowledge is necessary for understanding the roles of Cav 1.3 in developing and mature IHCs. Here, we describe age-dependent differences in the biophysical properties of Cav 1.3 channels in mouse IHCs. In mature IHCs, Cav 1.3 channels activate more rapidly and exhibit greater Ca ( 2+) -dependent inactivation (CDI) than in immature IHCs. Consistent with the properties of Cav 1.3 channels in heterologous expression systems, CDI in mature IHCs is not affected by increasing intracellular Ca ( 2+) buffering strength. However, CDI in immature IHCs is significantly reduced by strong intracellular Ca ( 2+) buffering, which both slows the onset of, and accelerates recovery from, inactivation. These results signify a developmental decline in the sensitivity of CDI to global elevations in Ca ( 2+) , which restricts negative feedback regulation of Cav 1.3 channels to incoming Ca ( 2+) ions in mature IHCs. Together with faster Cav 1.3 activation kinetics, increased reliance of Cav 1.3 CDI on local Ca ( 2+) may sharpen presynaptic Ca ( 2+) signals and improve temporal aspects of sound coding in mature IHCs.
authors.affiliation: Departments of Molecular Physiology and Biophysics, Otolaryngology-Head and Neck Surgery, and Neurology, University of Iowa, Iowa City, IA, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Inagaki
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type
keywords: Ca2+ channel; calmodulin; inner hair cell