Document Type
Article
Publication Date
6-22-2012
Description
The phosphoinositide 3-kinases (PI3K/Akt) dependent signaling pathway plays an important role in cardiac function, specifically cardiac contractility. We have reported that sepsis decreases myocardial Akt activation, which correlates with cardiac dysfunction in sepsis. We also reported that preventing sepsis induced changes in myocardial Akt activation ameliorates cardiovascular dysfunction. In this study we investigated the role of PI3K/Akt on cardiomyocyte function by examining the role of PI3K/Akt-dependent signaling on [Ca 2+]i, Ca2+ transients and membrane Ca2+ current, ICa, in cultured murine HL-1 cardiomyocytes. LY294002 (120 μM), a specific PI3K inhibitor, dramatically decreased HL-1 [Ca 2+]i, Ca2+ transients and ICa. We also examined the effect of PI3K isoform specific inhibitors, i.e. α (PI3-kinase α inhibitor 2; 28 nM); ? (TGX-221; 100 nM) and γ (AS-252424; 100 nM), to determine the contribution of specific isoforms to HL-1 [Ca 2+]i regulation. Pharmacologic inhibition of each of the individual PI3K isoforms significantly decreased [Ca2+]i, and inhibited Ca 2+ transients. Triciribine (120 μM), which inhibits AKT downstream of the PI3K pathway, also inhibited [Ca2+]i, and Ca 2+ transients and ICa. We conclude that the PI3K/Akt pathway is required for normal maintenance of [Ca2+]i in HL-1 cardiomyocytes. Thus, myocardial PI3K/Akt-PKB signaling sustains [Ca 2+]i required for excitation-contraction coupling in cardiomyoctyes.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Citation Information
Graves, Bridget M.; Simerly, Thomas; Li, Chuanfu; Williams, David L.; and Wondergem, Robert. 2012. Phosphoinositide-3-kinase/akt - Dependent Signaling is Required for Maintenance of [Ca2+]I,ICa, and Ca2+ Transients in HL-1 Cardiomyocytes. Journal of Biomedical Science. Vol.19(1). https://doi.org/10.1186/1423-0127-19-59 PMID: 22715995 ISSN: 1021-7770
Copyright Statement
© 2012 Graves et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.