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Updated: Jun 25, 2026
Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Molecular alteration of Ca(v)1.2 calcium channel in chronic myocardial infarction
Ping Liao1, Guang Li, De Jie Yu
1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
Abstract:
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 Delta9*/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*/Delta33 (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.
Insights
Calcium channel Ca(v)1.2 alternative splicing changes in myocardial infarction scar tissue. Novel channel variants were identified, potentially impacting cardiac function and arrhythmias.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Ion Channel Physiology
Background:
- Calcium channel Ca(v)1.2 is crucial for cardiac excitation-contraction coupling.
- Alternative splicing of Ca(v)1.2 channels generates diverse functional variants.
- Myocardial infarction (MI) can alter cardiac ion channel expression and function.
Purpose of the Study:
- To investigate changes in Ca(v)1.2 channel alternative splicing in a rat model of chronic myocardial infarction.
- To identify novel Ca(v)1.2 channel isoforms generated in the cardiac scar region.
- To determine the functional consequences of altered Ca(v)1.2 splicing on channel electrophysiology.
Main Methods:
- Rat model of myocardial infarction induced by coronary artery ligation.
- Reverse transcriptase polymerase chain reaction (RT-PCR) and laser capture microdissection to analyze alternative splicing.
- Immunostaining to localize specific Ca(v)1.2 channel variants in cardiac tissue.
- Heterologous expression in HEK293 cells and electrophysiological recordings (patch-clamp) to assess channel function.
Main Results:
- Significant alterations in alternatively spliced exon usage of Ca(v)1.2 channels were observed in the MI scar region.
- Increased inclusion of exon 9* and deletion of exon 33 were detected in surviving cardiomyocytes.
- A novel 9*/Delta33 Ca(v)1.2 channel isoform was generated in the scar region.
- Scar region Ca(v)1.2 channels exhibited hyperpolarized shifts in activation and inactivation potentials.
Conclusions:
- Chronic myocardial infarction induces significant changes in Ca(v)1.2 channel alternative splicing in the surviving cardiac tissue.
- Novel Ca(v)1.2 channel variants with altered electrophysiological properties are generated post-MI.
- These Ca(v)1.2 channel modifications may influence cardiac excitability, contractility, and potentially contribute to arrhythmogenesis.
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