Pacing-Induced Non-Uniform Ca²⁺ Dynamics in Rat Atria Revealed by Rapid-Scanning Confocal Microscopy

Abstract

Intracellular Ca²⁺ ([Ca²⁺]_i) dynamics in isolated myocytes differ between the atria and ventricles due to the distinct t-tubular distributions. Although cellular aspects of ventricular [Ca²⁺]_i dynamics in the heart have been extensively studied, little is known about those of atrial myocytes in situ. Here we visualized precise [Ca²⁺]_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 Ca²⁺ transients on systole among individual cells, whereas no discernible [Ca²⁺]_i elevation developed during diastole. In contrast, the remaining hearts showed non-uniform [Ca²⁺]_i dynamics within and among the cells especially under high-frequency (4 Hz) excitation, where subcellular cluster-like [Ca²⁺]_i rises or wave-like [Ca²⁺]_i propagation occurred on excitation. Such [Ca²⁺]_i inhomogeneity was more pronounced at high-frequency pacing, showing beat-to-beat Ca²⁺ transient alternans. Despite such non-uniform dynamics, cessation of burst pacing of the atria was not followed by emergence of spontaneous Ca²⁺ waves, indicating minor Ca²⁺-releasing potentials of the sarcoplasmic reticulum (SR). In summary, rat atria display a propensity to show non-uniform [Ca²⁺]_i dynamics on systole due to impaired Ca²⁺-release from the SR and paucity of t-tubules. Our results provide an important basis for understanding atrial pathophysiology.