Right atrial calcium homeostasis in a mouse model of obstructive sleep apnea

Atrial tachyarrhythmias, including atrial fibrillation (AF) and atrial flutter (AFL), are the most prevalent forms of arrhythmia and associate with atrial remodeling and calcium handling abnormalities. Obstructive sleep apnea (OSA) is linked with AF/AFL through poorly understood mechanisms. The objective of this study was to examine the inter-relationships between OSA and atrial calcium handling, and to test the hypothesis that atrial calcium homeostasis is altered in a mouse model of OSA induced by intermittent hypoxia (IH). Male wildtype C57BL/6 mice and both male and female mice with cardiomyocyte-specific expression of the GCaMP6f calcium indicator (GCaMP6f) were exposed to IH (n=9 C57BL/6; n=13 GCaMP6f) or room air (RA, n=10 C57BL/6; n=12 GCaMP6f) for eight weeks. Atrial and ventricular chamber weights (milligrams [mg], normalized to tibia length in millimeters [mm]) were obtained in C57BL/6 mice to assess hypertrophic remodeling. High-speed laser scanning confocal fluorescence microscopy was used in isolated perfused GCaMP6f hearts (1 millimolar calcium Krebs-Henseleit buffer with 40 micromolar blebbistatin) to assess atrial calcium transient amplitude and calcium reuptake kinetics. Measurements were obtained at sinus rhythm and during a pacing challenge (8 and 16 Hertz [Hz]). There were no differences in normalized right atrial weights (0.42±0.05 mg/mm IH versus 0.46±0.09 mg/mm RA, P=0.28) or normalized left atrial weights (0.33±0.07 mg/mm IH versus 0.30±0.05 mg/mm RA, P=0.32) between groups. However, normalized right ventricular weights were higher (1.5±0.1 mg/mm IH versus 1.3±0.2 mg/mm RA, P=0.04) while left ventricular weights were lower (3.6±0.3 mg/mm IH versus 4.1±0.5 mg/mm, P=0.03) in the IH than in the RA group. Fulton index, the ratio of right-ventricular weight to left-ventricle+septum weight, was higher in IH hearts (0.28±0.03 IH versus 0.24±0.03 RA, P=0.007), indicating right ventricular hypertrophy. In GCaMP6f hearts, sinus rhythm heart rate was higher in IH versus RA (306±30 beats per minute IH versus 273±39 beats per minute RA, P=0.03), and no differences in calcium transient amplitude were observed between the two groups at sinus rhythm (P=0.41) or at 8 Hz electric field stimulation (P=0.11). Cytosolic calcium decay rate was faster in IH versus RA at sinus rhythm (59±6 milliseconds [ms] IH versus 65±7 ms RA, P=0.04) but not at 8 Hz (39±2 ms IH versus 41±3 ms RA, P=0.15). However, during 16 Hz pacing, IH hearts displayed non-steady-state behavior including pro-arrhythmic calcium alternans (Alternans ratio of 0.42±0.38 IH versus 0.17±0.21 RA, P=0.05). Overall, our data reveal altered calcium homeostasis in a mouse model of OSA at high stimulation frequencies. This project was supported by MU Honors College and Peggy and Andrew Cherng, and by National Institutes of Health R01HL136292 (TD) and R01HL166617 (MB). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.