Abstract：
Sodium and potassium channels, especially Nav1.5 and Kir2.1, play key roles in the formation of action potentials in cardiomyocytes. These channels interact with, and are regulated by, synapse-associated protein 97 (SAP97). However, the regulatory role of SAP97 in myocyte remains incompletely understood. Here, we investigate the function of SAP97 phosphorylation in the regulation of Nav1.5 and Kir2.1 channel complexes and the upstream regulation of SAP97. We found that SAP97 is phosphorylated by casein kinase II (CK2) in vitro. In addition, transfection of casein kinase 2 interacting protein-1 (CKIP-1) into cardiomyocytes to drive CK2 from the nucleus to the cytoplasm, increased SAP97 phosphorylation and Nav1.5 and Kir2.1 current activity. These findings demonstrated that CKIP-1 modulates the subcellular translocation of CK2, which regulates Nav1.5 and Kir2.1 channel complex formation and activity in cardiomyocytes.
摘要：
钠和钾通道，特别是Nav1.5和Kir2.1在心肌细胞动作电位的形成中起关键作用。这些频道与，并受监管，突触相关蛋白97（SAP97）。然而,SAP97在肌细胞中的调节作用尚不完全清楚.这里,我们研究了SAP97磷酸化在Nav1.5和Kir2.1通道复合物的调节以及SAP97的上游调节中的功能。我们发现SAP97在体外被酪蛋白激酶II（CK2）磷酸化。此外,酪蛋白激酶2相互作用蛋白-1(CKIP-1)转染心肌细胞驱动CK2从细胞核到细胞质,增加SAP97磷酸化和Nav1.5和Kir2.1电流活性。这些发现表明，CKIP-1调节CK2的亚细胞易位，从而调节心肌细胞中Nav1.5和Kir2.1通道复合物的形成和活性。
