Atrial Granules in Atrial Cardiomyocytes as Acidic Calcium Stores

Abstract

Acidic calcium stores significantly influence basal calcium transient amplitude and β-adrenergic responses in cardiomyocytes. Atrial myocytes express a small acidic organelle called atrial granules (AG), which store and excrete atrial natriuretic peptide and are not expressed by healthy ventricular myocytes. AG are known to be acidic with a high calcium content. The number and position of these calcium-rich organelles relative to other signaling sites has not been investigated. Staining of acidic organelles in adult guinea pig cardiomyocytes showed the presence of fluorescent acidic puncta throughout the cytosol. Atrial myocytes exhibited an increased concentration of acidic organelles at the nuclear poles. Live cell fluorescent studies using PBA to inhibit peptidylglycine α-amidating monooxygenase, a crucial component of AG membranes, effectively eliminated staining at the nuclear poles and most acidic puncta in atrial cells. The application of PBA to ventricular myocytes did not affect LysoTracker staining. Electron microscopy studies on goat atrial fibrillation (AF) and sham control tissue, allowed visualization of AGs. Quantitative analysis revealed AGs to be in close apposition to the sarcoplasmic reticulum and mitochondria. AGs were significantly increased in AF goat samples when compared to sinus rhythm from 3D electron tomography images. Our imaging studies suggest that AGs make up a large percentage of atrial acidic stores, with AG associated with the sarcoplasmic reticulum and their number increasing during AF. We raise the question whether the positioning of AGs are strategic to communicate with other calcium organelles. Further studies to investigate whether AGs contribute to physiological calcium signalling are required.