PI3Kα in cardioprotection: Cytoskeleton, late Na(+) current, and mechanism of arrhythmias

PI 3-kinase α (PI3Kα) is a lipid kinase that converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). PI3Kα regulates a variety of cellular processes such as nutrient sensing, cell cycle, migration, and others. Heightened activity of PI3Kα in many types of cancer made it a prime oncology drug target, but also raises concerns of possible adverse effects on the heart. Indeed, recent advances in preclinical models demonstrate an important role of PI3Kα in the control of cytoskeletal integrity, Na(+) channel activity, cardioprotection, and prevention of arrhythmias.