AMPK‐mediated degradation of Nav1.5 through autophagy. Issue 4 (13th February 2019)

• Record Type: Journal Article
• Authors: Liu, Xuehua; Chen, Zheng; Han, Zhonglin; Liu, Yu; Wu, Xiang; Peng, Yuzhu; Di, Wencheng; Lan, Rongfang; Sun, Bugao; Xu, Biao; Xu, Wei
• Is Part Of: FASEB journal. Volume 33:Issue 4(2019)
• Page Start: 5366
• Page End: 5376
• Publication Date: 2019-02-13
• Subjects: sodium channel -- protein degradation -- SCN5A -- ischemia and reperfusion injury -- phosphorylation; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201801583RR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: The voltage‐gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down‐regulated by AMPK‐mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule‐associated protein 1 light chain 3 (LC3), by exposing the LC3‐interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.—Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. AMPK‐mediated degradation of Nav1.5 through autophagy. FASEB J. 33, 5366–5376 (2019). www.fasebj.org