The cost of publication in Journal of Biomedical Science is borne by the National Science Council, Taiwan.
Phosphoinositide-3-kinase/akt - dependent signaling is required for maintenance of [Ca2+]i, I Ca, and Ca2+ transients in HL-1 cardiomyocytes
1 Departments of Surgery, James H. Quillen College of Medicine, East Tennessee State Universitycpr, Johnson City, TN, 37614, USA
2 Departments of Biomedical Science, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA
3 Department of Physiology/Biomedical Science, James H. Quillen College of Medicine, East Tennessee State University, P.O. Box 70,576, Johnson City, TN, 37614-1708, USA
Journal of Biomedical Science 2012, 19:59 doi:10.1186/1423-0127-19-59Published: 20 June 2012
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 [Ca2+]i, Ca2+ transients and membrane Ca2+ current, ICa, in cultured murine HL-1 cardiomyocytes. LY294002 (1–20 μM), a specific PI3K inhibitor, dramatically decreased HL-1 [Ca2+]i, Ca2+ transients and ICa. We also examined the effect of PI3K isoform specific inhibitors, i.e. α (PI3-kinase α inhibitor 2; 2–8 nM); β (TGX-221; 100 nM) and γ (AS-252424; 100 nM), to determine the contribution of specific isoforms to HL-1 [Ca2+]i regulation. Pharmacologic inhibition of each of the individual PI3K isoforms significantly decreased [Ca2+]i, and inhibited Ca2+ transients. Triciribine (1–20 μM), which inhibits AKT downstream of the PI3K pathway, also inhibited [Ca2+]i, and Ca2+ 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 [Ca2+]i required for excitation-contraction coupling in cardiomyoctyes.