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The Journal of Neuroscience, October 18, 2006, 26(42):10690-10699; doi:10.1523/JNEUROSCI.2093-06.2006

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Cellular/Molecular
Alternative Splicing of the Ca_V1.3 Channel IQ Domain, a Molecular Switch for Ca²⁺-Dependent Inactivation within Auditory Hair Cells

Yiru Shen,¹ Dejie Yu,² Hakim Hiel,³ Ping Liao,¹ David T. Yue,^4,5 Paul A. Fuchs,³ and Tuck Wah Soong^1,2

¹Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, ²National Neuroscience Institute, Singapore 308443, ³Cochlear Neurotransmission Laboratory, Center for Hearing and Balance, Department of Otolaryngology, Head, and Neck Surgery, and Center for Sensory Biology, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, and Departments of ⁴Biomedical Engineering and ⁵Neuroscience, Ca²⁺ Signals Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Correspondence should be addressed to Tuck Wah Soong, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, 2 Medical Drive, Singapore 117597. Email: phsstw{at}nus.edu.sg

Native Ca_V1.3 channels within cochlear hair cells exhibit a surprising lack of Ca²⁺-dependent inactivation (CDI), given that heterologously expressed Ca_V1.3 channels show marked CDI. To determine whether alternative splicing at the C terminus of the Ca_V1.3 gene may produce a hair cell splice variant with weak CDI, we transcript-scanned mRNA obtained from rat cochlea. We found that the alternate use of exon 41 acceptor sites generated a splice variant that lost the calmodulin-binding IQ motif of the C terminus. These Ca_V1.3_IQ ("IQ deleted") channels exhibited a lack of CDI, which was independent of the type of coexpressed -subunits. Ca_V1.3_IQ channel immunoreactivity was preferentially localized to cochlear outer hair cells (OHCs), whereas that of Ca_V1.3_IQfull channels (IQ-possessing) labeled inner hair cells (IHCs). The preferential expression of Ca_V1.3_IQ within OHCs suggests that these channels may play a role in processes such as electromotility or activity-dependent gene transcription rather than neurotransmitter release, which is performed predominantly by IHCs in the cochlea.

Key words: alternative splicing; calcium channels; L-type calcium channels; splice variant; calcium-dependent inactivation; hair cells

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Received May 17, 2006; revised Aug. 30, 2006; accepted Aug. 30, 2006.

Correspondence should be addressed to Tuck Wah Soong, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, 2 Medical Drive, Singapore 117597. Email: phsstw{at}nus.edu.sg

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