Abstract 1605: T-Type Calcium Current Activates Pro-Survival Signaling Pathways after Myocardial Infarction
| Autor: | Naser Jaleel, Hajime Kubo, Erhe Gao, Scott MacDonnell, Xiongwen Chen, Hiroyuki Nakayama, David Angert, Timothy Flynn, Remus Berretta, Hongyu Zhang, Walter Koch, Jeffery Molkentin, Steven Houser |
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| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Circulation. 118 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.118.suppl_18.s_356 |
| Popis: | Ca 2+ influx through L-type Ca 2+ channels (I Ca,L ) is essential for cardiac contraction and for activation of a variety of Ca 2+ dependent signaling pathways. However, Ca 2+ can also enter cardiac myocytes through T-type Ca 2+ channels (TTCCs), which are found in the fetal heart and become re-expressed in adult ventricular myocytes (VMs) during cardiac pathology. While excess I Ca,L promotes VM death and dysfunction, the role of Ca 2+ influx through TTCCs (I Ca,T ) in cardiac stress responses is unknown and is the topic of this study. METHODS: Transgenic (TG) mice with inducible, cardiac-specific expression of α1G-TTCCs and control (CTR) mice were used. Myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. Mice were sacrificed at 1 week and 7 weeks post-MI. RESULTS: TG hearts had greater in vivo fractional shortening (FS) than CTR (TG: 39.6±3.2%, N=16 vs CTR: 32.2±1.2%, N=14; pCa,T of −32.8±3.0 pA/pF. I Ca,L was smaller in TG than in CTR VMs (−9.6±0.7 pA/pF vs −12.0±0.4 pA/pF, p< 0.05). Compared to I Ca,L , I Ca,T triggered smaller Ca 2+ transients (1.5±0.1 vs 2.1±0.1, n=10; p2+ influx than CTR hearts, TG hearts showed no cardiac histopathology or premature death, and TG hearts had higher levels of phosphorylated Akt (p CONCLUSION: Ca 2+ influx via TTCCs has small effects on cardiac contraction, but is associated with reduced infarct size and increased survival, suggesting that it induces cytoprotective signaling. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia). |
| Databáze: | OpenAIRE |
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