AMPK activation with AICAR provokes an acute fall in plasma [K+].
AMPK activation with AICAR provokes an acute fall in plasma [K+].
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AICAR 激活 AMPK 会引起血浆浓度急剧下降 [K]。
DOI：
10.1152/ajpcell.00464.2007
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
McDonough,AliciaA
中科院分区：
文献类型：
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作者：
Zheng,Dan;Perianayagam,Anjana;Lee,DonnaH;Brannan,MDouglas;Yang,LiE;Tellalian,David;Chen,Pei;Lemieux,Kathleen;Marette,André;Youn,JangH;McDonough,AliciaA
AMP 激活蛋白激酶 (AMPK) 通过细胞内 AMP 与 ATP 比率的增加而激活，刺激可恢复 ATP 水平的途径。我们测试了 AMPK 激活影响细胞外液 (ECF) K+ 稳态的假设。在清醒的大鼠中，通过输注 5-氨基咪唑-4-甲酰胺-1-β-d-呋喃核苷 (AICAR) 激活 AMPK：38.4 mg/kg 推注，然后输注 4 mg·kg−1·min−1。血浆 [K+] 和 [葡萄糖] 在 AICAR 输注 1 小时后均下降，[K+] 在 3 小时内下降至 3.3 ± 0.04 mM，与肌肉 AMPK 磷酸化的增加呈线性相关。 AICAR 治疗不会增加尿 K+ 排泄。无论血浆 [K+] 长期升高还是降低，AICAR 都会降低 [K+]。在 AICAR 输注 120 至 180 分钟之间，维持基线血浆 [K+] 所需的 K+ 输注速率达到 15.7 ± 1.3 μmol K+·kg−1·min−1。在肌肉中表达 AMPK 的显性抑制形式 (Tg-KD1) 的小鼠中，基线 [K+] 与对照 (4.2 ± 0.1 mM) 没有差异，但响应 AICAR (0.25 g/kg) 的血浆 [K+] 下降减弱：对照中的 [K+] 降至 3.6 ± 0.1，Tg-KD1 中降至 3.9 ± 0.1 mM，这表明 ECF K+ 至少部分地重新分配至肌肉 ICF。总之，这些发现表明，用 AICAR 激活 AMPK 活性会引起血浆 [K+] 显着下降，并提出一种将 K+ 从 ECF 重新分配到 ICF 的新机制。
AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K+homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg/kg bolus then 4 mg·kg−1·min−1infusion. Plasma [K+] and [glucose] both dropped at 1 h of AICAR infusion and [K+] dropped to 3.3 ± 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K+excretion. AICAR lowered [K+] whether plasma [K+] was chronically elevated or lowered. The K+infusion rate needed to maintain baseline plasma [K+] reached 15.7 ± 1.3 μmol K+·kg−1·min−1between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K+] was not different from controls (4.2 ± 0.1 mM), but the fall in plasma [K+] in response to AICAR (0.25 g/kg) was blunted: [K+] fell to 3.6 ± 0.1 in controls and to 3.9 ± 0.1 mM in Tg-KD1, suggesting that ECF K+redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K+] and suggest a novel mechanism for redistributing K+from ECF to ICF.