Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca2+ Currents via Increased PI3Kα/PKB Signaling

Ca influx through the L-type Ca channel (ICa,L) is a key determinant of cardiac contractility and is modulated by multiple signaling pathways. Because the regulation of ICa,L by phosphoinositide-3-kinases (PI3Ks) and phosphoinositide-3-phosphatase (PTEN) is unknown, despite their involvement in the regulation of myocardial growth and contractility, ICa,L was recorded in myocytes isolated from mice overexpressing a dominant-negative p110α mutant (DN-p110α) in the heart, lacking the PI3Kγ gene (PI3Kγ) or with muscle-specific ablation of PTEN (PTEN). Combinations of these genetically altered mice were also examined. Although there were no differences in the expression level of CaV1.2 proteins, basal ICa,L densities were larger (P