Department of Biomedicine, Aarhus University, Denmark.
J Appl Physiol (1985). 2012 Jun;112(12):2057-67. doi: 10.1152/japplphysiol.01558.2011. Epub 2012 Apr 5.
Electrical stimulation of isolated muscles may lead to membrane depolarization, gain of Na(+), loss of K(+) and fatigue. These effects can be counteracted with β(2)-agonists possibly via activation of the Na(+)-K(+) pumps. Anoxia induces loss of force; however, it is not known whether β(2)-agonists affect force and ion homeostasis in anoxic muscles. In the present study isolated rat extensor digitorum longus (EDL) muscles exposed to anoxia showed a considerable loss of force, which was markedly reduced by the β(2)-agonists salbutamol (10(-6) M) and terbutaline (10(-6) M). Intermittent stimulation (15-30 min) clearly increased loss of force during anoxia and reduced force recovery during reoxygenation. The β(2)-agonists salbutamol (10(-7)-10(-5) M) and salmeterol (10(-6) M) improved force development during anoxia (25%) and force recovery during reoxygenation (55-262%). The effects of salbutamol on force recovery were prevented by blocking the Na(+)-K(+) pumps with ouabain or by blocking glycolysis with 2-deoxyglucose. Dibutyryl cAMP (1 mM) or theophylline (1 mM) also improved force recovery remarkably. In anoxic muscles, salbutamol decreased intracellular Na(+) and increased (86)Rb uptake and K(+) content, indicating stimulation of the Na(+)-K(+) pumps. In fatigued muscles salbutamol induced recovery of excitability. Thus β(2)-agonists reduce the anoxia-induced loss of force, leading to partial force recovery. These data strongly suggest that this effect is mediated by cAMP stimulation of the Na(+)-K(+) pumps and that it is not related to recovery of energy status (PCr, ATP, lactate).
电刺激分离肌肉可能导致膜去极化、钠离子内流、钾离子外流和疲劳。这些效应可以被β2-激动剂对抗，可能是通过激活钠钾泵来实现的。缺氧会导致肌力丧失；然而，目前还不清楚β2-激动剂是否会影响缺氧肌肉的肌力和离子稳态。在本研究中，暴露于缺氧的分离大鼠趾长伸肌（EDL）表现出相当大的肌力丧失，而β2-激动剂沙丁胺醇（10-6 M）和特布他林（10-6 M）明显减少了这种丧失。间歇性刺激（15-30 分钟）明显增加了缺氧过程中的肌力丧失，并减少了复氧过程中的肌力恢复。β2-激动剂沙丁胺醇（10-7-10-5 M）和沙美特罗（10-6 M）改善了缺氧过程中的肌力发展（25%）和复氧过程中的肌力恢复（55-262%）。沙丁胺醇对肌力恢复的作用被哇巴因阻断钠钾泵或 2-脱氧葡萄糖阻断糖酵解所阻止。二丁酰环腺苷酸（1 mM）或茶碱（1 mM）也显著改善了肌力恢复。在缺氧肌肉中，沙丁胺醇降低了细胞内钠离子浓度，增加了（86）Rb 摄取和钾离子含量，表明钠钾泵被刺激。在疲劳肌肉中，沙丁胺醇诱导了兴奋性的恢复。因此，β2-激动剂减少了缺氧引起的肌力丧失，导致部分肌力恢复。这些数据强烈表明，这种效应是通过 cAMP 刺激钠钾泵介导的，与能量状态（PCr、ATP、乳酸）的恢复无关。
