Title: Spatiotemporal Profiles of Sarcoplasmic Reticulum Ca2+ Release in Mouse Atrial Cardiomyoctes in situ
Abstract: Previous studies in atrial cardiomyocytes isolated from various mammalian species have demonstrated poorly developed transverse(t)-tubules and inhomogeneities of sarcoplasmic reticulum (SR) Ca2+ release, but little is known of mice. Here, we examined the t-tubular organization and action potential-evoked Ca2+ release in in situ myocytes, using confocal microscopy of Langendorff-perfused hearts. Imaging of ANNINE-6plus-stained sarcolemmal membranes revealed paucity of t-tubules in atrial, but densely and regularly spaced t-tubules in ventricular myocytes. However, both myocyte types exhibited regular, striated appearance of type 2 ryanodine receptor distribution. Line-scans (2 ms/line) across multiple myocytes obtained during sinus rhythm from fluo-4 loaded hearts revealed homogeneous [Ca2+]i increases in ventricular myocytes, whereas atrial myocytes exhibited areas with delayed transients (see Figure). Histograms of F50values (the time to 50% of peak F/F0 [where F indicates fluorescence intensity, and F0 indicates F at rest]) for the subsarcolemmal (SS) and central (C) compartments in ventricular myocytes were largely congruent, whereas the corresponding atrial histograms did not superimpose and exhibited multiple peaks. Thus, major myocyte-to-myocyte differences in the spatial organization of SR Ca2+ release exist among in situ mouse atrial myocytes, likely reflecting non-uniform t-tubule distribution.