Pacing-induced non-uniform ca(2+) dynamics in rat atria revealed by rapid-scanning confocal microscopy

Intracellular Ca(2+) ([Ca(2+)]i) dynamics in isolated myocytes differ between the atria and ventricles due to the distinct t-tubular distributions. Although cellular aspects of ventricular [Ca(2+)]i dynamics in the heart have been extensively studied, little is known about those of atrial myocytes in situ. Here we visualized precise [Ca(2+)]i dynamics of atrial myocytes in Langendorff-perfused rat hearts by rapid-scanning confocal microscopy. Of 16 fluo-4-loaded hearts imaged during pacing up to 4-Hz, five hearts showed spatially uniform Ca(2+) transients on systole among individual cells, whereas no discernible [Ca(2+)]i elevation developed during diastole. In contrast, the remaining hearts showed non-uniform [Ca(2+)]i dynamics within and among the cells especially under high-frequency (4 Hz) excitation, where subcellular cluster-like [Ca(2+)]i rises or wave-like [Ca(2+)]i propagation occurred on excitation. Such [Ca(2+)]i inhomogeneity was more pronounced at high-frequency pacing, showing beat-to-beat Ca(2+) transient alternans. Despite such non-uniform dynamics, cessation of burst pacing of the atria was not followed by emergence of spontaneous Ca(2+) waves, indicating minor Ca(2+)-releasing potentials of the sarcoplasmic reticulum (SR). In summary, rat atria display a propensity to show non-uniform [Ca(2+)]i dynamics on systole due to impaired Ca(2+)-release from the SR and paucity of t-tubules. Our results provide an important basis for understanding atrial pathophysiology.