期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 458, 期 4, 页码 701-711出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-009-0652-4
关键词
Alternative splicing; Ca(v)1.2 channel; Myocardial infarction
类别
资金
- Biomedical Research Council of Singapore
Ca(v)1.2 channels are important for excitation-contraction coupling of cardiac muscles. Alternative splicing of Ca(v)1.2 channels could produce extensive phenotypic variations of channel properties. In a rat model of chronic myocardial infarction, we investigated whether Ca(v)1.2 channels may alter the use of alternatively spliced exons to generate functional variants. A myocardial infarction model on rat was generated by ligating the left anterior descending artery. Eight weeks after ligation, we found that in the scar region, the expression of a number of alternatively spliced exons were changed. The proportions of exon 9* inclusion and exon 33 deletion were detected to increase and localize at the surviving cardiac muscle cells with reverse transcriptase polymerase chain reaction, laser capture microdissection, and immunostaining. The wild-type Delta 9*/33 (deletion of exon 9* and inclusion of exon 33) channel was reduced greatly in the scar region and several other isoforms increased. Importantly, a novel 9*/Delta 33 (inclusion of exon 9* and deletion of exon 33) channel was generated in the scar region. Electrophysiological studies showed that the channels found in scar region exhibited hyperpolarized shifts in both the activation and inactivation potentials when expressed in HEK293 cells. The changes of Ca(v)1.2 channels may play a role either in maintenance of muscle excitability and contractility or contribute to arrhythmogenesis.
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