PDF(Pubmed)
Abstract：
UNASSIGNED: 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 IIδ (CaMKIIδ), 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.
UNASSIGNED: 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.
UNASSIGNED: OSA was induced in C57BL/6 wild-type and CaMKIIδ-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.
UNASSIGNED: 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 CaMKIIδ-knockout mice were protected. Accordingly, the rate of spontaneous Ca2+ release events increased in the wild-type PTFE mice while being impeded in the CaMKIIδ-knockout mice.
UNASSIGNED: Atrial Na+ concentration and propensity for spontaneous Ca2+ release events were higher in an OSA mouse model in a CaMKIIδ-dependent manner, which could have therapeutic implications.
UNASSIGNED: 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.
UNASSIGNED: OSA was induced in C57BL/6 wild-type and CaMKIIδ-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.
UNASSIGNED: 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 CaMKIIδ-knockout mice were protected. Accordingly, the rate of spontaneous Ca2+ release events increased in the wild-type PTFE mice while being impeded in the CaMKIIδ-knockout mice.
UNASSIGNED: Atrial Na+ concentration and propensity for spontaneous Ca2+ release events were higher in an OSA mouse model in a CaMKIIδ-dependent manner, which could have therapeutic implications.
摘要：
■阻塞性睡眠呼吸暂停（OSA）与各种病理有关，包括心律失常，如心房颤动。OSA的具体治疗选择主要限于对症治疗。我们先前表明，活性氧（ROS）的产生增加通过Ca2/钙调蛋白依赖性蛋白激酶IIδ（CaMKIIδ）通过电压依赖性Na通道刺激晚期钠电流，从而增加心律失常的倾向。然而,对心房细胞内Na+稳态的影响从未被证实。此外，患者通常表现出广泛的合并症，这使得很难确定OSA单独的影响。
■我们分析了OSA对ROS产生的影响，胞质Na+水平，从无合并症的OSA小鼠模型中分离出的心房心肌细胞中的自发性心律失常率。
■通过将聚四氟乙烯（PTFE）注射到舌头中，在C57BL/6野生型和CaMKIIδ敲除小鼠中诱导了OSA。8周后,通过激光扫描共聚焦显微镜分析其心房心肌细胞的胞浆和线粒体ROS的产生.通过落射荧光显微镜对胞质Na浓度和心律失常进行定量。
■PTFE处理导致胞浆和线粒体ROS产生增加。重要的是,在PTFE处理的小鼠中，细胞溶质Na+浓度在各种刺激频率下急剧增加，而CaMKIIδ敲除小鼠受到保护。因此，在野生型PTFE小鼠中，自发Ca2释放事件的速率增加，而在CaMKIIδ敲除小鼠中受到阻碍。
■在OSA小鼠模型中，心房Na浓度和自发Ca2+释放事件的倾向以CaMKIIδ依赖性方式较高，可能有治疗意义。
■我们分析了OSA对ROS产生的影响，胞质Na+水平，从无合并症的OSA小鼠模型中分离出的心房心肌细胞中的自发性心律失常率。
■通过将聚四氟乙烯（PTFE）注射到舌头中，在C57BL/6野生型和CaMKIIδ敲除小鼠中诱导了OSA。8周后,通过激光扫描共聚焦显微镜分析其心房心肌细胞的胞浆和线粒体ROS的产生.通过落射荧光显微镜对胞质Na浓度和心律失常进行定量。
■PTFE处理导致胞浆和线粒体ROS产生增加。重要的是,在PTFE处理的小鼠中，细胞溶质Na+浓度在各种刺激频率下急剧增加，而CaMKIIδ敲除小鼠受到保护。因此，在野生型PTFE小鼠中，自发Ca2释放事件的速率增加，而在CaMKIIδ敲除小鼠中受到阻碍。
■在OSA小鼠模型中，心房Na浓度和自发Ca2+释放事件的倾向以CaMKIIδ依赖性方式较高，可能有治疗意义。
