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Changes in Cochlear PMCA2 Expression Correlate with the Maturation of Auditory Sensitivity

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ABSTRACT

The plasma membrane Ca2+ ATPase 2 (PMCA2) is necessary for auditory transduction and serves as the primary Ca2+ extrusion mechanism in auditory stereocilia bundles. To date, studies examining PMCA2 in auditory function using mutant mice have focused on the phenotype of late adolescent and adult mice. Here, we focus on the changes of PMCA2 in the maturation of auditory sensitivity by comparing auditory responses to RNA and protein expression levels in haploinsufficient PMCA2 and wild-type mice from P16 into adulthood. Auditory sensitivity in wild-type mice improves between P16 and 3 weeks of age, when it becomes stable through adolescence. In haploinsufficient mice, there are frequency-dependent loss of sensitivity and subsequent recovery of thresholds between P16 and adulthood. RNA analysis demonstrates that α-Atp2b2 transcript levels increase in both wild-type and heterozygous cochleae between P16 and 5 weeks. The increases reported for the α-Atp2b2 transcript type during this stage in development support the requisite usage of this transcript for mature auditory transduction. PMCA2 expression also increases in wild-type cochleae between P16 and 5 weeks suggesting that this critical auditory protein may be involved in normal maturation of auditory sensitivity after the onset of hearing. We also characterize expression levels of two long noncoding RNA genes, Gm15082 (lnc82) and Gm15083 (lnc83), which are transcribed on the opposite strand in the 5′ region of Atp2b2 and propose that the lnc83 transcript may be involved in regulating α-Atp2b2 expression.

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ACKNOWLEDGMENTS

We would like to thank L. Robinson for maintaining our mouse colonies and V. Street for comments on the manuscript. This work was supported by grants from the NIH; RO1 DC02739 (BLT), P30 DC04661 (BLT), T32 DC005361 (CJW and RRM), and T32 DC000033 (CJW).

Disclosure

The authors declare that they have no conflicts of interest, financial or otherwise, regarding this work.

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Authors and Affiliations

  1. Department of Otolaryngology—Head and Neck Surgery, University of Washington, Box 356515, Seattle, WA, 98195, USA

    Claire J. Watson & Bruce L Tempel

  2. Department of Speech and Hearing Sciences, University of Washington, 1417 NE 42nd St., Seattle, WA, 98105, USA

    Sarah M. Lies

  3. Department of Pharmacology, University of Washington, Box 357280, Seattle, WA, 98195, USA

    Claire J. Watson, Rebecca R. Minich & Bruce L Tempel

  4. The Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA, 98195, USA

    Claire J. Watson, Sarah M. Lies, Rebecca R. Minich & Bruce L Tempel

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  1. Claire J. Watson
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Correspondence to Bruce L Tempel.

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Watson, C.J., Lies, S.M., Minich, R.R. et al. Changes in Cochlear PMCA2 Expression Correlate with the Maturation of Auditory Sensitivity. JARO 15, 543–554 (2014). https://doi.org/10.1007/s10162-014-0454-z

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  • DOI: https://doi.org/10.1007/s10162-014-0454-z

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