Atrial local Ca 2+ signaling and inositol 1,4,5-trisphosphate receptors

Abstract

In atrial myocytes lacking t-tubules, action potential triggers junctional Ca 2+ releases in the cell periphery, which propagates into the cell interior. The present article describes growing evidence on atrial local Ca 2+ signaling and on the functions of inositol 1,4,5-trisphosphate receptors (IP 3Rs) in atrial myocytes, and show our new findings on the role of IP 3R subtype in the regulation of spontaneous focal Ca 2+ releases in the compartmentalized areas of atrial myocytes. The Ca 2+ sparks, representing focal Ca 2+ releases from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR) clusters, occur most frequently at the peripheral junctions in isolated resting atrial cells. The Ca 2+ sparks that were darker and longer lasting than peripheral and non-junctional (central) sparks, were found at peri-nuclear sites in rat atrial myocytes. Peri-nuclear sparks occurred more frequently than central sparks. Atrial cells express larger amounts of IP 3Rs compared with ventricular cells and possess significant levels of type 1 IP 3R (IP 3R1) and type 2 IP 3R (IP 3R2). Over the last decade the roles of atrial IP 3R on the enhancement of Ca 2+-induced Ca 2+ release and arrhythmic Ca 2+ releases under hormonal stimulations have been well documented. Using protein knock-down method and confocal Ca 2+ imaging in conjunction with immunocytochemistry in the adult atrial cell line HL-1, we could demonstrate a role of IP 3R1 in the maintenance of peri-nuclear and non-junctional Ca 2+ sparks via stimulating a posttranslational organization of RyR clusters.