Ros in Cardiac Calcium Signaling

Abstract

ROS in cardiac calcium signaling Reactive oxygen species (ROS) play important roles in physiologic and pathophysiologic signaling within diverse cells including cardiac myocytes. Here we examine the rapid application of extracellular H2O2 (100 uM) to examine how this ROS reagent affects Ca2+ signaling in single isolated cardiac ventricular myocytes. Single mouse ventricular myocytes were examined with a confocal microscope and found to have a robust, reversible increase in the Ca2+ spark rate. In quiescent cells this increase in the Ca2+ spark rate was associated with a decrease in the SR Ca2+ content. This is consistent with the increase in the SR Ca2+ leak (as evidenced by the increase in the Ca2+ spark rate) that followed the H2O2 application. Since ROS has been shown to activate other signaling systems in heart (e.g. CaMKII), the interactions between H2O2 dependent ROS elevation and both CaMKII and PKA were examined. While significant interactions between rapid, transient ROS elevation and CaMKII and PKA were observed, it was also determined that the actions of these ROS elevations on Ca2+ sparks was not mediated by either CaMKII or PKA. How ROS may affect EC coupling under these conditions is also examined and discussed.