Alternative splicing of the Ca(v)1.3 channel IQ domain, a molecular switch for Ca2+-dependent inactivation within auditory hair cells.
Native Ca(V)1.3 channels within cochlear hair cells exhibit a surprising lack of Ca2+-dependent inactivation (CDI), given that heterologously expressed Ca(V)1.3 channels show marked CDI. To determine whether alternative splicing at the C terminus of the Ca(V)1.3 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(V)1.3(IQdelta) ("IQ deleted") channels exhibited a lack of CDI, which was independent of the type of coexpressed beta-subunits. Ca(V)1.3(IQdelta) channel immunoreactivity was preferentially localized to cochlear outer hair cells (OHCs), whereas that of Ca(V)1.3(IQfull) channels (IQ-possessing) labeled inner hair cells (IHCs). The preferential expression of Ca(V)1.3(IQdelta) 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.
Shen
Yiru
Y
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Yu
Dejie
D
Hiel
Hakim
H
Liao
Ping
P
Yue
David T
DT
Fuchs
Paul A
PA
Soong
Tuck Wah
TW
D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics*; D003051:Cochlea / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats
D015220:Calcium Channels; C093712:Cacna1d protein, rat; D002118:Calcium