The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels
The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels
复制标题
DOI：
10.1016/j.neuropharm.2013.03.022
复制
发表时间：
2013-12-01
影响因子：
4.7
通讯作者：
Saez, Juan C.
中科院分区：
文献类型：
--
作者：
Riquelme, Manuel A.;Cea, Luis A.;Saez, Juan C.
在骨骼肌的重复刺激过程中，细胞外ATP水平升高，激活嘌呤能受体，增加Ca 2+内流，并增强收缩力，这种反应称为增强。我们发现，ATP似乎是通过泛连接蛋白1半通道（Panx 1 HC）释放的。免疫细胞化学分析和功能是一致的pannexin 1本地化与二氢吡啶和ryanodine受体插入慢（比目鱼肌）和快（趾长伸肌，EDL）肌肉的T-小管。分离的肌纤维在电刺激期间摄取乙锭（Etd（+））并释放小分子（如ATP）。与两种葡萄糖摄取途径一致，诱导摄取的2-NBDG，一种荧光葡萄糖衍生物，通过抑制HC或葡萄糖转运蛋白（GLUT 4）而降低，并通过双重阻断而阻断。成人骨骼肌显然不表达连接蛋白，使得连接蛋白半通道不太可能有助于小分子的摄取和释放。重复电刺激诱导的ATP释放、Etd（+）摄取和增强作用被HC阻断剂阻断，并且在pannexin 1敲除小鼠的肌肉中没有发生。MRS 2179是一种P2 Y（1）R阻断剂，可阻止EDL的增强作用，但对比目鱼肌没有影响，这表明在快肌中，ATP激活P2 Y（1）受体，但不激活P2 X受体。在增强过程中，pannexin 1的丝氨酸和苏氨酸残基的磷酸化增加，可能介导HC开放。在重复激活过程中打开Panx 1 HC允许ATP流出，葡萄糖流入，可能还有Ca 2+，这是增强收缩所必需的。这篇文章是题为“缝隙连接通道和半通道的当前药理学”的特刊部分的一部分。(C)2013爱思唯尔有限公司保留所有权利。
During repetitive stimulation of skeletal muscle, extracellular ATP levels raise, activating purinergic receptors, increasing Ca2+ influx, and enhancing contractile force, a response called potentiation. We found that ATP appears to be released through pannexin1 hemichannels (Panx1 HCs). Immunocytochemical analyses and function were consistent with pannexin1 localization to T-tubules intercalated with dihydropyridine and ryanodine receptors in slow (soleus) and fast (extensor digitorum longus, EDL) muscles. Isolated myofibers took up ethidium (Etd(+)) and released small molecules (as ATP) during electrical stimulation. Consistent with two glucose uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter (GLUT4), and blocked by dual blockade. Adult skeletal muscles apparently do not express connexins, making it unlikely that connexin hemichannels contribute to the uptake and release of small molecules. ATP release, Etd(+) uptake, and potentiation induced by repetitive electrical stimulation were blocked by HC blockers and did not occur in muscles of pannexin1 knockout mice. MRS2179, a P2Y(1)R blocker, prevented potentiation in EDL, but not soleus muscles, suggesting that in fast muscles ATP activates P2Y(1) but not P2X receptors. Phosphorylation on Ser and Thr residues of pannexin1 was increased during potentiation, possibly mediating HC opening. Opening of Panx1 HCs during repetitive activation allows efflux of ATP, influx of glucose and possibly Ca2+ too, which are required for potentiation of contraction.This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. (C) 2013 Elsevier Ltd. All rights reserved.