RT Journal Article
SR Electronic
T1 Alternative Splicing of the Ca<sub>V</sub>1.3 Channel IQ Domain, a Molecular Switch for Ca<sup>2+</sup>-Dependent Inactivation within Auditory Hair Cells
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10690
OP 10699
DO 10.1523/JNEUROSCI.2093-06.2006
VO 26
IS 42
A1 Yiru Shen
A1 Dejie Yu
A1 Hakim Hiel
A1 Ping Liao
A1 David T. Yue
A1 Paul A. Fuchs
A1 Tuck Wah Soong
YR 2006
UL http://www.jneurosci.org/content/26/42/10690.abstract
AB Native CaV1.3 channels within cochlear hair cells exhibit a surprising lack of Ca2+-dependent inactivation (CDI), given that heterologously expressed CaV1.3 channels show marked CDI. To determine whether alternative splicing at the C terminus of the CaV1.3 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 CaV1.3IQΔ (“IQ deleted”) channels exhibited a lack of CDI, which was independent of the type of coexpressed β-subunits. CaV1.3IQΔ channel immunoreactivity was preferentially localized to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing) labeled inner hair cells (IHCs). The preferential expression of CaV1.3IQΔ 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.