Alternative splicing of the Ca _V 1 .2 calcium channel and its role in cardiovascular diseases

The L‐type calcium channel Ca _V 1.2 serves as a core trigger for excitation‐contraction and excitation‐transcription coupling in cardiovascular cells. Its abnormalities are closely linked to multiple cardiovascular diseases, including hypertension, arrhythmias, and cardiac hypertrophy. Alternative splicing (AS) generates Ca _V 1.2 channel isoforms with distinct electrophysiological properties and drug sensitivity, finely tuning channel functions. This review systematically summarizes AS regulation and pathological significance of Ca _V 1.2 in the cardiovascular system. Three key splicing events, mutually exclusive exons 8/8a, cassette exon 9* and exon 33, impact channel gating, calcium influx, and drug responsiveness. These AS events are dynamically regulated by splicing factors such as Rbfox1/2, PTBP1, and RBM20. We further analyze aberrant Ca _V 1.2 splicing in hypertension, heart failure, myocardial infarction, and diabetic cardiomyopathy. Finally, we discuss preclinical and clinical advances of antisense oligonucleotides for treating cardiovascular Ca _V 1.2 channelopathies. This review aims to clarify the regulatory network of Ca _V 1.2 AS, providing theoretical evidence for precision therapies based on splicing modulation.