Hegner, Philipp and Ofner, Florian and Schaner, Benedikt and Gugg, Mathias and Trum, Maximilian and Lauerer, Anna-Maria and Maier, Lars Siegfried and Arzt, Michael and Lebek, Simon and Wagner, Stefan (2024) CaMKIIδ-dependent dysregulation of atrial Na<SUP>+</SUP> homeostasis promotes pro-arrhythmic activity in an obstructive sleep apnea mouse model. FRONTIERS IN PHARMACOLOGY, 15: 1411822. ISSN , 1663-9812
Full text not available from this repository. (Request a copy)Abstract
Background: Obstructive sleep apnea (OSA) has been linked to various pathologies, including arrhythmias such as atrial fibrillation. Specific treatment options for OSA are mainly limited to symptomatic approaches. We previously showed that increased production of reactive oxygen species (ROS) stimulates late sodium current through the voltage-dependent Na+ channels via Ca2+/calmodulin-dependent protein kinase II delta (CaMKII delta), thereby increasing the propensity for arrhythmias. However, the impact on atrial intracellular Na+ homeostasis has never been demonstrated. Moreover, the patients often exhibit a broad range of comorbidities, making it difficult to ascertain the effects of OSA alone. Objective: We analyzed the effects of OSA on ROS production, cytosolic Na+ level, and rate of spontaneous arrhythmia in atrial cardiomyocytes isolated from an OSA mouse model free from comorbidities. Methods: OSA was induced in C57BL/6 wild-type and CaMKII delta-knockout mice by polytetrafluorethylene (PTFE) injection into the tongue. After 8 weeks, their atrial cardiomyocytes were analyzed for cytosolic and mitochondrial ROS production via laser-scanning confocal microscopy. Quantifications of the cytosolic Na+ concentration and arrhythmia were performed by epifluorescence microscopy. Results: PTFE treatment resulted in increased cytosolic and mitochondrial ROS production. Importantly, the cytosolic Na+ concentration was dramatically increased at various stimulation frequencies in the PTFE-treated mice, while the CaMKII delta-knockout mice were protected. Accordingly, the rate of spontaneous Ca2+ release events increased in the wild-type PTFE mice while being impeded in the CaMKII delta-knockout mice. Conclusion: Atrial Na+ concentration and propensity for spontaneous Ca2+ release events were higher in an OSA mouse model in a CaMKII delta-dependent manner, which could have therapeutic implications.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POSITIVE AIRWAY PRESSURE; HEART-FAILURE; KINASE-II; FIBRILLATION; CONTRACTILITY; ASSOCIATION; MECHANISMS; ARRHYTHMIA; OXIDATION; EVENTS; sleep-disordered breathing; reactive oxygen species; CaMKII delta; Na+ homeostasis; cardiac arrhythmias; obstructive sleep apnea |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Aug 2025 05:40 |
| Last Modified: | 04 Aug 2025 05:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63885 |
Actions (login required)
 |
View Item |
