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- Title
Alternative Splicing of L-type CaV1.2 Calcium Channels: Implications in Cardiovascular Diseases.
- Authors
Zhenyu Hu; Mui Cheng Liang; Tuck Wah Soong
- Abstract
L-type CaV1.2 calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alteration of CaV1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands CaV1.2 channel structures to modify function, pharmacological and biophysical property such as calcium/voltage-dependent inactivation (C/VDI), or to influence its post-translational modulation by interacting proteins such as Galectin-1. Alternative splicing has generated functionally diverse CaV1.2 isoforms that can be developmentally regulated in the heart, or under pathophysiological conditions such as in heart failure. More importantly, alternative splicing of certain exons of CaV1.2 has been reported to be regulated by splicing factors such as RNA-binding Fox-1 homolog 1/2 (Rbfox 1/2), polypyrimidine tract-binding protein (PTBP1) and RNA-binding motif protein 20 (RBM20). Understanding how CaV1.2 channel function is remodelled in disease will provide better information to guide the development of more targeted approaches to discover therapeutic agents for cardiovascular diseases.
- Subjects
KNOTS &; splices; CALCIUM channels; CARDIOVASCULAR diseases; EXONS (Genetics); GALECTINS
- Publication
Genes, 2017, Vol 8, Issue 12, p344
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes8120344