Dysregulated Ca2+ cycling in atrial fibrillation.
Dysregulated Ca2+ cycling in atrial fibrillation.
复制标题
心房颤动中 Ca2 循环失调。
DOI：
10.1093/eurheartj/ehad099
复制
发表时间：
2023
影响因子：
39.3
通讯作者：
VanWagoner,DavidR
中科院分区：
文献类型：
--
作者：
Rennison,JulieH;VanWagoner,DavidR
心房收缩受细胞内钙水平调节；这反映了钙流入、固存和流出的平衡。去甲肾上腺素（内源性）或异丙肾上腺素（药理学）激活β -肾上腺素能增加腺苷酸环化酶的活性，增加cAMP水平和蛋白激酶A （PKA）活性。cAMP的降解是由磷酸二酯酶（PDEs）调控的。相关PKA靶点的磷酸化状态，如l型钙通道（LTCC）、肌浆网Ca2+- atp酶（SERCA2a）和肌丝蛋白，受PKA活性和磷酸酶活性平衡的调节。在没有房颤（AF）或发作性房颤（pAF）病史的患者中，关键LTCC亚基的基础磷酸化高于慢性（持续性）房颤患者的心房肌细胞14 Pavlidou等人14提供的新证据表明，这可能是由于慢性房颤患者中磷酸二酯酶异构体8B，变体2 （PDE8B2）的丰富度和活性增加所致。
Atrial contractility is regulated by intracellular calcium levels; these reflect the balance of calcium influx, sequestration, and efflux. Beta-adrenergic activation with either norepinephrine (endogenous) or isoproterenol (pharmacological) increases the activity of adenylate cyclase, increasing cAMP levels and protein kinase A (PKA) activity. Degradation of cAMP is regulated by phosphodiesterases (PDEs). The phosphorylation state of relevant PKA targets, such as the L-type calcium channel (LTCC), the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and myofilament proteins, is regulated by the balance of PKA activity and phosphatase activity. In patients with no history of atrial fibrillation (AF) or paroxysmal AF (pAF), basal phosphorylation of key LTCC subunits is higher than in atrial myocytes from patients with chronic (persistent) AF. 14 Pavlidou et al. 14 provide novel evidence that this is probably due to increased abundance and activity of phosphodiesterase isoform 8B, variant 2 (PDE8B2), in patients with chronic AF.