Premium
AMPK‐mediated degradation of Nav1.5 through autophagy
Author(s) -
Liu Xuehua,
Chen Zheng,
Han Zhonglin,
Liu Yu,
Wu Xiang,
Peng Yuzhu,
Di Wencheng,
Lan Rongfang,
Sun Bugao,
Xu Biao,
Xu Wei
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801583rr
Subject(s) - ampk , autophagy , nav1.5 , chemistry , protein kinase a , activator (genetics) , microbiology and biotechnology , sodium channel , kinase , biology , biochemistry , sodium , apoptosis , receptor , organic chemistry
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