Atrial local Ca2+ signaling and inositol 1,4,5-trisphosphate receptors

In atrial myocytes lacking t-tubules, action potential triggers junctional Ca2+ releases in the cell periphery, which propagates into the cell interior. The present article describes growing evidence on atrial local Ca2+ signaling and on the functions of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) in atrial myocytes, and show our new findings on the role of IP3R subtype in the regulation of spontaneous focal Ca2+ releases in the compartmentalized areas of atrial myocytes. The Ca2+ sparks, representing focal Ca2+ 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 Ca2+ sparks that were darker and longer lasting than peripheral and non-junctional (central) sparks, were found at pen-nuclear sites in rat atrial myocytes. Peri-nuclear sparks occurred more frequently than central sparks. Atrial cells express larger amounts of IP(3)Rs compared with ventricular cells and possess significant levels of type 1 IP3R (IP(3)R1) and type 2 IP3R (IP(3)R2). Over the last decade the roles of atrial IP3R on the enhancement of Ca2+-induced Ca2+ release and arrhythmic Ca2+ releases under hormonal stimulations have been well documented. Using protein knockdown method and confocal Ca2+ imaging in conjunction with immunocytochemistry in the adult atrial cell line HL-1, we could demonstrate a role of IP(3)R1 in the maintenance of pen-nuclear and non-junctional Ca2+ sparks via stimulating a posttranslational organization of RyR clusters. (C) 2010 Elsevier Ltd. All rights reserved.