Distinct α2 Na,K-ATPase membrane pools are differently involved in early skeletal muscle remodeling during disuse.
Distinct α2 Na,K-ATPase membrane pools are differently involved in early skeletal muscle remodeling during disuse.
复制标题
DOI：
10.1085/jgp.201511494
复制
发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Krivoi II
中科院分区：
文献类型：
--
作者：
Kravtsova VV;Petrov AM;Matchkov VV;Bouzinova EV;Vasiliev AN;Benziane B;Zefirov AL;Chibalin AV;Heiny JA;Krivoi II
位置，位置，位置。骨骼肌的钠钾泵在神经肌肉接头处受到不同的调节。Na，K-ATP酶是骨骼肌收缩功能所必需的，它表达Na，K-ATP酶的α1和α2亚基亚型。α2同工酶在成人骨骼肌中占优势，与非收缩肌相比，对工作的贡献更大。后肢悬吊是一种广泛应用的肌肉废用模型，可导致姿势性骨骼肌进行性萎缩。本研究检测了急性（6-12 h）HS对大鼠比目鱼肌（废用）和膈肌（收缩）Na，K-ATP酶α1和α2同工酶功能的影响。急性废用对大鼠比目鱼肌Na，K-ATP酶α2同工酶产电活性、蛋白质和mRNA含量的动态和亚型特异性调节早期废用诱导的重塑事件还包括磷膜蛋白磷酸化及其丰度增加和与α2 Na，K-ATP酶的相关性。α2 Na，K-ATP酶活性的丧失导致产电泵转运减少和静息膜电位去极化。α2 Na，K-ATP酶活性降低是由酶活性降低引起的，而不是由蛋白质和mRNA含量改变、肌膜定位或与烟碱乙酰胆碱受体的功能相互作用引起的。连接外α2 Na，K-ATP酶活性的丧失强烈地依赖于肌肉的使用，即使HS 12 h后该膜区域蛋白质和mRNA含量的增加以及α2 Na，K-ATP酶丰度的增加也不能抵消这种持续的抑制。相反，在HS期间，其他因素可能调节能够恢复的连接α2 Na，K-ATP酶池的亚群。值得注意的是，急性低强度肌肉负荷恢复了α2 Na，K-ATP酶池的功能。这些结果表明，大鼠骨骼肌α2 Na，K-ATP酶受肌肉运动的动态和急性调节，并首次证明α2 Na，K-ATP酶的连接池和连接外池受到不同的调节。
Location, location, location. The Na-K pump of skeletal muscle is regulated differently at neuromuscular junctions. The Na,K-ATPase is essential for the contractile function of skeletal muscle, which expresses the α1 and α2 subunit isoforms of Na,K-ATPase. The α2 isozyme is predominant in adult skeletal muscles and makes a greater contribution in working compared with noncontracting muscles. Hindlimb suspension (HS) is a widely used model of muscle disuse that leads to progressive atrophy of postural skeletal muscles. This study examines the consequences of acute (6–12 h) HS on the functioning of the Na,K-ATPase α1 and α2 isozymes in rat soleus (disused) and diaphragm (contracting) muscles. Acute disuse dynamically and isoform-specifically regulates the electrogenic activity, protein, and mRNA content of Na,K-ATPase α2 isozyme in rat soleus muscle. Earlier disuse-induced remodeling events also include phospholemman phosphorylation as well as its increased abundance and association with α2 Na,K-ATPase. The loss of α2 Na,K-ATPase activity results in reduced electrogenic pump transport and depolarized resting membrane potential. The decreased α2 Na,K-ATPase activity is caused by a decrease in enzyme activity rather than by altered protein and mRNA content, localization in the sarcolemma, or functional interaction with the nicotinic acetylcholine receptors. The loss of extrajunctional α2 Na,K-ATPase activity depends strongly on muscle use, and even the increased protein and mRNA content as well as enhanced α2 Na,K-ATPase abundance at this membrane region after 12 h of HS cannot counteract this sustained inhibition. In contrast, additional factors may regulate the subset of junctional α2 Na,K-ATPase pool that is able to recover during HS. Notably, acute, low-intensity muscle workload restores functioning of both α2 Na,K-ATPase pools. These results demonstrate that the α2 Na,K-ATPase in rat skeletal muscle is dynamically and acutely regulated by muscle use and provide the first evidence that the junctional and extrajunctional pools of the α2 Na,K-ATPase are regulated differently.