title: Dynamic alterations in the CaV1.2/CaM/CaMKII signaling pathway in the left ventricular myocardium of ischemic rat hearts.
abstract: Cardiac L-type calcium channel (CaV1.2), calmodulin (CaM), and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) form the CaV1.2/CaM/CaMKII signaling pathway, which plays an important role in maintaining intracellular Ca(2+) homeostasis. The roles of CaM and CaMKII in the regulation of CaV1.2 in Ca(2+)-dependent inactivation and facilitation have been reported; however, alterations in this signaling pathway in the heart after myocardial ischemia (MI) had not been well characterized. In this study, we investigated the dynamic changes in CaV1.2, CaM, and CaMKII mRNA and protein expression levels in the left ventricles of the heart following MI in rats. The MI model was induced by ligating the left anterior descending coronary artery; the rats were divided into the following five groups: the 6 h post-MI group (MI-6h), 24 h post-MI group (MI-24h), 1 week post-MI group (MI-1w), 2 weeks post-MI group (MI-2w), and the sham group. The mRNA levels were measured by quantitative real-time polymerase chain reaction and the protein expression was determined by western blotting and immunohistochemistry. There were no observable differences in the CaV1.2 mRNA and protein levels at the early stages of MI, but these levels decreased at MI-2w. Both the mRNA and protein levels of CaM increased at MI-6h, peaked at MI-24h, and then reduced to normal levels at MI-2w. CaMKII mRNA and protein levels decreased at MI-6h and reached their lowest level at MI-24h. Taken together, these data demonstrate that there are dynamic changes in the CaV1.2/CaM/CaMKII signaling pathway following MI injuries, which suggests that different therapeutic regimens should be used at different time points after MI injuries.
authors.affiliation: 1 Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University , Shenyang, People's Republic of China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Hu
authors.forename: De-Ri
authors.initials: DR
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Xue-Fei
authors.initials: XF
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Hao
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; D012333:RNA, Messenger; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2