What You Did Not Know About Cardiac Ca2+ Handling: Lysosomes and Oxidized PKA.

3 PKA (protein kinase A) is a critical signaling molecule in cardiomyocytes, involved in calcium (Ca 2+) handling, gene transcription, and metabolism. First, in contrast to previous reports, 13,14 PKARI disulfide formation did not appear to influence the catalytic activity of PKA, nor did it alter phosphorylation of established PKA targets involved in cardiac Ca 2+ handling. B, Phosphorylation of the TPC prevents Ca 2+ release and limits Ca 2+ -induced Ca 2+ release from the ryanodine receptor (RyR). First, the authors set out to determine whether PKARI oxidation occurs during I/R. Using human atrial tissue obtained before and after cardioplegic arrest, as well as murine heart samples after I/R, the authors discovered that I/R injury significantly increased PKARI oxidation and disulfide formation. [Extracted from the article]