Molecular alteration of Ca(v)1.2 calcium channel in chronic myocardial infarction.
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.
Liao
Ping
P
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
Li
Guang
G
Yu
De Jie
DJ
Yong
Tan Fong
TF
Wang
Jue Jin
JJ
Wang
Jing
J
Soong
Tuck Wah
TW
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002908:Chronic Disease; D008297:Male; D009154:Mutation / Q000235:genetics; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics*; D017682:Myocardial Stunning / Q000209:etiology / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C)