Atrial Specific Stretch-Dependent Sub-Cellular Ca2+ Signaling

Abstract

Atrial myocytes undergo stretch during diastole as do ventricular myocytes. We have recently identified a novel mechanism that links cellular stretch in ventricular myocytes to the tuning of Ca2+ release from the sarcoplasmic reticulum (SR)(Prosser et al. Science 2011;333:1440-5). This mechanism, “X-ROS signaling”, depends on NOX2 (NADPH oxidase) in the sarcolemmal and transverse tubule (TT) membranes to generate reactive oxygen species (ROS), which appears to oxidize the nearby (nanometers) ryanodine receptors (SR Ca2+ release channels) and increases their sensitivity to [Ca2+]i. Stretch mediates X-ROS signaling through microtubules, which appear to interact with NOX2 to enable it to generate ROS. We evaluated the effect of acute and repeated stretch on sub-cellular Ca2+ sparks in murine atrial myocytes (C57/B6; Figure 1A). Ca2+ sparks were recorded before and after stretch (8% of cell length). Ca2+ spark frequency increased during stretch and returned to pre-stretch values during relaxation (Figure 1B). Thus, X-ROS signaling and the consequent stretch-dependent Ca2+ release “tuning” found in ventricular myocytes is also operative in atrial myocytes. We will present data on the importance of NOX2, TTs and other components of the X-ROS signaling pathway in health and disease in atrial myocytes.