Phosphoinositide-3-kinase/akt - dependent signaling is required for maintenance of [Ca<sup>2+</sup>]<sub>i,</sub><it>I</it><sub>Ca</sub>, and Ca<sup>2+</sup> transients in HL-1 cardiomyocytes

Phosphoinositide-3-kinase/akt - dependent signaling is required for maintenance of [Ca<sup>2+</sup>]<sub>i,</sub><it>I</it><sub>Ca</sub>, and Ca<sup>2+</sup> transients in HL-1 cardiomyocytes

<p>Abstract</p> <p>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 s...

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Bibliographic Details
Main Authors: Graves Bridget M, Simerly Thomas, Li Chuanfu, Williams David L, Wondergem Robert
Format: Article
Language:English
Published: BMC 2012-06-01
Series:Journal of Biomedical Science
Subjects:
Calcium
Fura-2
Phosphoinositide-3-kinase/Akt
HL-1 cardiomyocytes
Whole-cell voltage clamp
Electrophysiology
Online Access:http://www.jbiomedsci.com/content/19/1/59
Description
Summary:<p>Abstract</p> <p>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<sup>2+</sup>]<sub>i</sub>, Ca<sup>2+</sup> transients and membrane Ca<sup>2+</sup> current, <it>I</it><sub>Ca</sub>, in cultured murine HL-1 cardiomyocytes. LY294002 (1–20 μM), a specific PI3K inhibitor, dramatically decreased HL-1 [Ca<sup>2+</sup>]<sub>i</sub>, Ca<sup>2+</sup> transients and <it>I</it><sub>Ca</sub>. We also examined the effect of PI3K isoform specific inhibitors, <it>i.e.</it> 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 [Ca<sup>2+</sup>]<sub>i</sub> regulation. Pharmacologic inhibition of each of the individual PI3K isoforms significantly decreased [Ca<sup>2+</sup>]<sub>i</sub>, and inhibited Ca<sup>2+</sup> transients. Triciribine (1–20 μM), which inhibits AKT downstream of the PI3K pathway, also inhibited [Ca<sup>2+</sup>]<sub>i</sub>, and Ca<sup>2+</sup> transients and <it>I</it><sub>Ca</sub>. We conclude that the PI3K/Akt pathway is required for normal maintenance of [Ca<sup>2+</sup>]<sub>i</sub> in HL-1 cardiomyocytes. Thus, myocardial PI3K/Akt-PKB signaling sustains [Ca<sup>2+</sup>]<sub>i</sub> required for excitation-contraction coupling in cardiomyoctyes.</p>
ISSN:1021-7770
1423-0127

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