Key result
Alternative splicing of CaV1.2 channels links to cardiovascular disease and provides theoretical precision therapy targets.
Why the study?
Abnormalities of the CaV1.2 channel are linked to cardiovascular diseases, but the regulatory network and pathological role of its alternative splicing needed systematic clarification.
Alternative splicing of the CaV1.2 calcium channel plays a critical role in cardiovascular diseases and presents a potential target for precision therapies using antisense oligonucleotides.
Hypothesis-generating for CaV1.2 splicing-targeted therapies in CVD; leaves open clinical translation without further validation.
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.
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Wang et al. (2026) conducted a review in Cardiovascular diseases. Alternative splicing of CaV1.2 was evaluated. Alternative splicing of the CaV1.2 calcium channel regulates channel functions and is implicated in cardiovascular diseases, providing theoretical evidence for precision therapies.
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