Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M111.268722
Title: Alternative splicing at C terminus of Ca v1.4 calcium channel modulates calcium-dependent inactivation, activation potential, and current density
Authors: Tan, G.M.Y.
Yu, D.
Wang, J.
Soong, T.W. 
Issue Date: 6-Jan-2012
Citation: Tan, G.M.Y., Yu, D., Wang, J., Soong, T.W. (2012-01-06). Alternative splicing at C terminus of Ca v1.4 calcium channel modulates calcium-dependent inactivation, activation potential, and current density. Journal of Biological Chemistry 287 (2) : 832-847. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M111.268722
Abstract: The Ca V1.4 voltage-gated calcium channel is predominantly expressed in the retina, and mutations to this channel have been associated with human congenital stationary night blindness type-2. The L-type Ca V1.4 channel displays distinct properties such as absence of calcium-dependent inactivation (CDI) and slow voltage-dependent inactivation (VDI) due to the presence of an autoinhibitory domain (inhibitor of CDI) in the distal C terminus. We hypothesized that native Ca V1.4 is subjected to extensive alternative splicing, much like the other voltage-gated calcium channels, and employed the transcript scanning method to identify alternatively spliced exons within the Ca V1.4 transcripts isolated from the human retina. In total, we identified 19 alternative splice variations, of which 16 variations have not been previously reported. Characterization of the C terminus alternatively spliced exons using whole-cell patch clamp electrophysiology revealed a splice variant that exhibits robust CDI. This splice variant arose from the splicing of a novel alternate exon (43*) that can be found in 13.6% of the full-length transcripts screened. Inclusion of exon 43*inserts a stop codon that truncates half the C terminus. The Ca V1.443*channel exhibited robust CDI, a larger current density, a hyperpolarized shift in activation potential by ∼10 mV, and a slower VDI. Through deletional experiments, we showed that the inhibitor of CDI was responsible for modulating channel activation and VDI, in addition to CDI. Calcium currents in the photoreceptors were observed to exhibit CDI and are more negatively activated as compared with currents elicited from heterologously expressed full-length Ca V1.4. Naturally occurring alternative splice variants may in part contribute to the properties of the native Ca V1.4 channels. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/108252
ISSN: 00219258
DOI: 10.1074/jbc.M111.268722
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

35
checked on Sep 10, 2019

WEB OF SCIENCETM
Citations

29
checked on Sep 10, 2019

Page view(s)

63
checked on Sep 7, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.