Copyright © 2005, European Society of Cardiology
Splicing for alternative structures of Cav1.2 Ca2+ channels in cardiac and smooth muscles
aNational Neuroscience Institute, Singapore 308433, Singapore
bDepartment of Physiology, Faculty of Medicine, National University of Singapore, Blk MD9, 2 Medical Drive, Singapore 117597, Singapore
cDepartment of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
dDepartment of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
* Corresponding author. Department of Physiology, Faculty of Medicine, National University of Singapore, Blk MD9, 2 Medical Drive, Singapore 117597, Singapore. Tel.: +65 68741938; fax: +65 67788161. Email address: tuck_wah_soong{at}nni.com.sg
An estimate of up to 60% of genes are subjected to alternative splicing, and 15% of human genetic diseases are associated with mutation of the splice sites [Krawczak M, Reiss J, and Cooper DN. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet 1992; 90: 41–54; Cooper TA, and Mattox W. The regulation of splice-site selection, and its role in human disease. Am J Hum Genet 1997; 61: 259–66; Modrek B and Lee CJ. Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nat Genet 2003; 34: 177–80; Modrek B, Resch A, Grasso C, and Lee C. Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res 2001; 29: 2850–9; Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860–921] [1–5]. The molecular diversity of alternatively spliced transcripts provides templates for a myriad of protein structures that are potentially crucial to sustaining the complexity of human physiology. The extensive alternative splicing of the 
11.2-subunit of the L-type Cav1.2 channel, producing splice variants with distinct electrophysiological and pharmacological properties, would impact directly on the function of the cardiovascular system. Cell-selective expression of Cav1.2 channels containing a specific alternatively spliced exon increases the functional variations for specific cellular activities in response to changing physiological signals. However, the regulation or control of the 11.2-subunit alternative splicing machinery is unknown, and the role of numerous splice variants expressed in a cell is a mystery. A systematic and concerted effort is required to determine all the possible combinations of alternatively spliced exons in 11.2-subunits in smooth and cardiac muscles. This will provide useful information to monitor changes on the usage of the entire suite of alternatively spliced exons to help relate altered Cav1.2 channel function to physiology and disease.
KEYWORDS Alternative splicing; Calcium channel; Cardiovascular
Tme for primary review 23 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Liao, D. Yu, G. Li, T. F. Yong, J. L. Soon, Y. L. Chua, and T. W. Soong A Smooth Muscle Cav1.2 Calcium Channel Splice Variant Underlies Hyperpolarized Window Current and Enhanced State-dependent Inhibition by Nifedipine J. Biol. Chem., November 30, 2007; 282(48): 35133 - 35142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cheng, J. Liu, M. Asuncion-Chin, E. Blaskova, J. P. Bannister, A. M. Dopico, and J. H. Jaggar A Novel CaV1.2 N Terminus Expressed in Smooth Muscle Cells of Resistance Size Arteries Modifies Channel Regulation by Auxiliary Subunits J. Biol. Chem., October 5, 2007; 282(40): 29211 - 29221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Tringham, C. E. Payne, J. R. B. Dupere, and M. M. Usowicz Maturation of rat cerebellar Purkinje cells reveals an atypical Ca2+ channel current that is inhibited by {omega}-agatoxin IVA and the dihydropyridine (-)-(S)-Bay K8644 J. Physiol., February 1, 2007; 578(3): 693 - 714. [Abstract] [Full Text] [PDF]
|
|