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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.

SUBMITTER: Inagaki A

PROVIDER: S-EPMC3710344 | biostudies-literature | 2013 May-Jun

REPOSITORIES: biostudies-literature

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Developmental alterations in the biophysical properties of Ca(v) 1.3 Ca(2+) channels in mouse inner hair cells.

Inagaki Akira A Lee Amy A

Channels (Austin, Tex.) 20130319 3

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 h ...[more]

PMID: 23510940

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Project description:Key pointsAge-related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age-related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9-12 kHz cochlear region) decreases by about 30-40% with age. The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23-repaired mice (C57BL/6NTacCdh23+ ), indicating that it could contribute to the different progression of hearing loss among mouse strains. The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains.AbstractInner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age-related hearing loss. Here, we have investigated the functional characteristics of IHCs from early-onset hearing loss mice harbouring the allele Cdh23ahl (C57BL/6J and C57BL/6NTac), from late-onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23ahl mutation (C57BL/6NTacCdh23+ ) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9-12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30-40% starting from ∼6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTacCdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres re-form functional axon-somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post-synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re-establishing the LOC-IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23ahl allele but not in C57BL/6NTacCdh23+ mice, indicating that the MET apparatus directly contributes to the progression of age-related hearing loss.

Dataset Information

Developmental alterations in the biophysical properties of Ca(v) 1.3 Ca(2+) channels in mouse inner hair cells.

Publications

Developmental alterations in the biophysical properties of Ca(v) 1.3 Ca(2+) channels in mouse inner hair cells.

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