Alternative Splicing of L-type Ca(V)1.2 Calcium Channels: Implications in Cardiovascular Diseases

L-type Ca(V)1.2 calcium channels are the major pathway for Ca(2+) influx to initiate the contraction of smooth and cardiac muscles. Alteration of Ca(V)1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands Ca(V)1.2 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 Ca(V)1.2 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 Ca(V)1.2 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 Ca(V)1.2 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.