Control of microvascular PO2 kinetics following onset of muscle contractions: role for AMPK
Control of microvascular PO2 kinetics following onset of muscle contractions: role for AMPK
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DOI：
10.1152/ajpregu.00294.2011
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发表时间：
2011-11-01
影响因子：
2.8
通讯作者：
Ezaki, Osamu
中科院分区：
文献类型：
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作者：
Kano, Yutaka;Poole, David C.;Ezaki, Osamu
[10]杨文，杨文.肌肉收缩后微血管PO 2动力学的控制：AMPK的作用。Am J Physiol Regul Integr Comp Physiol 301：R1350-R1357，2011年。首次发表于2011年8月17日; doi：10.1152/ajpregu.00294.2011。运动开始后的微血管氧分压（Pmv（O2））动力学反映了肌肉O-2输送和摄取之间的关系（V/dotO（2））。虽然AMP活化蛋白激酶（AMPK）被认为是线粒体和一氧化氮代谢的调节剂，但运动开始时O-2输送和（V）/dotO（2）的动态平衡是否依赖于AMPK活化水平尚不清楚。我们使用肌肉特异性AMPK显性阴性（AMPK-DN）转基因小鼠来研究骨骼肌AMPK对肌肉收缩开始后Pmv（O2）动力学的作用。使用磷光猝灭技术测量静息时以及过渡到抽搐（1 Hz）和强直时的Pmv（O2）（100 Hz，3-5 V，4 ms脉冲持续时间，刺激持续时间为100 ms，每1 s，持续1 min）腓肠肌收缩（每组n = 6）的AMPK-DN小鼠和野生型同窝仔（WT）在异氟烷麻醉下用100%吸入O-2以避免低氧血症。收缩前Pmv（O2）两组间无显著差异（P > 0.05）。这两种肌肉收缩条件下表现出延迟，然后指数下降Pmv（O2）。然而，与WT相比，AMPK-DN显示1）Pmv（O2）开始下降之前的时间延迟延长（1 Hz：WT，3.2 +/- 0.5 s; AMPK-DN，6.5 +/- 0.4 s; 100 Hz：WT，4.4 +/- 1.0 s; AMPK-DN，6.5 +/- 1.4 s; P < 0.05），2）更快的响应时间（即，时间常数; 1 Hz：WT，19.4 +/- 3.9 s; AMPK-DN，12.4 +/- 2.6 s; 100 Hz：WT，15.1 +/- 2.2 s; AMPK-DN，9.0 +/- 1.7 s; P < 0.05）。这些发现与AMPK-DN小鼠中大量线粒体和微血管功能障碍的存在一致，这可能减缓O-2消耗动力学（即，氧化磷酸化反应）并在收缩开始时损害充血反应，从而播下运动不耐受的种子。
Kano Y, Poole DC, Sudo M, Hirachi T, Miura S, Ezaki O. Control of microvascular PO2 kinetics following onset of muscle contractions: role for AMPK. Am J Physiol Regul Integr Comp Physiol 301: R1350-R1357, 2011. First published August 17, 2011; doi:10.1152/ajpregu.00294.2011.-The microvascular partial pressure of oxygen (Pmv(O2)) kinetics following the onset of exercise reflects the relationship between muscle O-2 delivery and uptake ((V) over dotO(2)). Although AMP-activated protein kinase (AMPK) is known as a regulator of mitochondria and nitric oxide metabolism, it is unclear whether the dynamic balance of O-2 delivery and (V) over dotO(2) at exercise onset is dependent on AMPK activation level. We used transgenic mice with muscle-specific AMPK dominant-negative (AMPK-DN) to investigate a role for skeletal muscle AMPK on Pmv(O2) kinetics following onset of muscle contractions. Phosphorescence quenching techniques were used to measure Pmv(O2) at rest and across the transition to twitch (1 Hz) and tetanic (100 Hz, 3-5 V, 4-ms pulse duration, stimulus duration of 100 ms every 1 s for 1 min) contractions in gastrocnemius muscles (each group n = 6) of AMPK-DN mice and wild-type littermates (WT) under isoflurane anesthesia with 100% inspired O-2 to avoid hypoxemia. Baseline Pmv(O2) before contractions was not different between groups (P > 0.05). Both muscle contraction conditions exhibited a delay followed by an exponential decrease in Pmv(O2). However, compared with WT, AMPK-DN demonstrated 1) prolongation of the time delay before Pmv(O2) began to decline (1 Hz: WT, 3.2 +/- 0.5 s; AMPK-DN, 6.5 +/- 0.4 s; 100 Hz: WT, 4.4 +/- 1.0 s; AMPK-DN, 6.5 +/- 1.4 s; P < 0.05), 2) a faster response time (i.e., time constant; 1 Hz: WT, 19.4 +/- 3.9 s; AMPK-DN, 12.4 +/- 2.6 s; 100 Hz: WT, 15.1 +/- 2.2 s; AMPK-DN, 9.0 +/- 1.7 s; P < 0.05). These findings are consistent with the presence of substantial mitochondrial and microvascular dysfunction in AMPK-DN mice, which likely slows O-2 consumption kinetics (i.e., oxidative phosphorylation response) and impairs the hyperemic response at the onset of contractions thereby sowing the seeds for exercise intolerance.