Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle
Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle
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DOI：
10.1152/ajpcell.00361.2009
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发表时间：
2010-06-01
影响因子：
5.5
通讯作者：
Nielsen, Ole Baekgaard
中科院分区：
文献类型：
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作者：
Broch-Lips, Martin;Pedersen, Thomas Holm;Nielsen, Ole Baekgaard
Broch-Lips M，Pedersen Th，Nielsen OB。嘌呤能受体激活对去极化骨骼肌Na+-K+泵活性、兴奋性和功能的影响。Am J Physiol Cell Physiol 298：C1438-C1444,2010。2010年3月3日首次出版；doi：10.1152/ajpcell.00361.2009。-活性诱导的胞外嘌呤和嘧啶的升高与许多组织中的自分泌和旁分泌信号有关。在这里，我们研究了嘌呤能信号对去极化骨骼肌兴奋性和收缩能力的影响。通过将细胞外K+从4 mM提高到10 mM，实验上降低了肌肉的兴奋性，使强直力降低到4 mM K+时的24+/-2%。然而，当增加1 mM三磷酸腺苷时，力恢复到控制力的65+/-8%(P<；0.001，n=5)。ADP也有类似的恢复，但UTP或腺苷没有。P2Y(1)受体拮抗剂(3mU M SCH-202676或1U M MRS-2500)可抑制三磷酸腺苷诱导的肌力恢复。M波面积增加4倍表明，ATP诱导的力量恢复与肌肉兴奋性的恢复有关(P<；0.05，n=4)。用Rb-86(+)作为K+示踪剂的实验表明，ATP还使肌肉Na+-K+泵的活性增加了一倍。磷脂酶C抑制剂U-73122可抑制肌力恢复和三磷酸腺苷对Na~+-K~+泵活性的刺激。结论：嘌呤能信号可增加去极化骨骼肌Na+-K+泵活性，改善肌力和兴奋性。这种新的嘌呤能调节对于在剧烈运动中维持肌肉兴奋性可能是重要的，因为在剧烈运动中，细胞外K+可以显著增加。
Broch-Lips M, Pedersen TH, Nielsen OB. Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle. Am J Physiol Cell Physiol 298: C1438-C1444, 2010. First published March 3, 2010; doi:10.1152/ajpcell.00361.2009.-Activity- induced elevation of extracellular purines and pyrimidines has been associated with autocrine and paracrine signaling in many tissues. Here we investigate the effect of purinergic signaling for the excitability and contractility of depolarized skeletal muscle. Muscle excitability was experimentally depressed by elevating the extracellular K+ from 4 to 10 mM, which reduced the tetanic force to 24 +/- 2% of the force at 4 mM K+. Upon addition of 1 mM ATP, however, the force recovered to 65 +/- 8% of the control force (P < 0.001, n = 5). A similar recovery was seen with ADP, but not with UTP or adenosine. The ATP-induced force recovery could be inhibited by P2Y(1) receptor antagonists (3 mu M SCH-202676 or 1 mu M MRS-2500). A fourfold increase in M-wave area demonstrated that the ATP-induced force recovery was associated with restoration of muscle excitability (P < 0.05, n = 4). Experiments using Rb-86(+) as a tracer for K+ showed that ATP also induced a twofold increase in the activity of muscle Na+-K+ pumps. The force recovery and the stimulation of the Na+-K+ pump activity by ATP were inhibited by 50 mu M of the phospholipase C inhibitor U-73122. It is concluded that purinergic signaling can increase the Na+-K+ pump activity and improve force and excitability of depolarized skeletal muscles. This novel purinergic regulation may be important for the maintenance of muscle excitability during intense exercise, where the extracellular K+ can increase substantially.