Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States.
Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States; Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, 90 Chilam, Jinju 660-751, Republic of Korea.
Respir Physiol Neurobiol. 2014 May 1;195:19-26. doi: 10.1016/j.resp.2014.01.020. Epub 2014 Feb 13.
Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca(2+) concentration ([Ca(2+)]i). Recent studies suggest that AMP-activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting the background K(+) channels such as TASK. Here we studied the effects of modulators of AMPK on TASK activity in cell-attached patches. Activators of AMPK (1mM AICAR and 0.1-0.5mM A769662) did not inhibit TASK activity or cause depolarization during acute (10min) or prolonged (2-3h) exposure. Hypoxia inhibited TASK activity by ∼70% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15-40min) failed to increase [Ca(2+)]i in glomus cells. Compound C (40μM), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylated AMPKα in PC12 cells, and Compound C blocked the phosphorylation. Our results suggest that AMPK does not affect TASK activity and is not involved in hypoxia-induced elevation of intracellular [Ca(2+)] in isolated rat carotid body glomus cells.
急性缺氧会使颈动脉体化学感受器（球）细胞去极化，并升高细胞内 Ca(2+)浓度([Ca(2+)]i)。最近的研究表明，AMP 激活的蛋白激酶（AMPK）通过抑制背景 K(+)通道（如 TASK）来介导缺氧的这些作用。在这里，我们研究了 AMPK 调节剂对细胞贴附斑中 TASK 活性的影响。AMPK 的激活剂（1mM AICAR 和 0.1-0.5mM A769662）在急性（10min）或延长（2-3h）暴露期间不会抑制 TASK 活性或导致去极化。在 AICAR 或 A769662 预处理的细胞中，缺氧抑制 TASK 活性约 70%。AICAR 和 A769662（15-40min）均未能增加球细胞中的 [Ca(2+)]i。AMPK 的抑制剂 Compound C（40μM）对缺氧诱导的 TASK 抑制没有影响。AICAR 和 A769662 在 PC12 细胞中磷酸化 AMPKα，而 Compound C 则阻断了磷酸化。我们的结果表明，AMPK 不影响 TASK 活性，也不参与分离的大鼠颈动脉体球细胞中缺氧诱导的细胞内 [Ca(2+)]i 升高。
