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

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(3)Rs) in atrial myocytes, and show our new findings on the role of IP(3)R 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(3)Rs compared with ventricular cells and possess significant levels of type 1 IP(3)R (IP(3)R1) and type 2 IP(3)R (IP(3)R2). Over the last decade the roles of atrial IP(3)R 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(3)R1 in the maintenance of peri-nuclear and non-junctional Ca(2+) sparks via stimulating a posttranslational organization of RyR clusters.