Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation
Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation
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DOI：
10.1074/jbc.m313932200
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发表时间：
2004-07-02
影响因子：
4.8
通讯作者：
Bernheim, L
中科院分区：
文献类型：
--
作者：
Konig, S;Hinard, V;Bernheim, L
人们普遍认为肌生成素是骨骼肌分化最早可检测到的标志物之一。本研究表明，在人成肌细胞分化过程中，一个内向整流K+通道（Kir2.1）及其相关的超极化触发了肌生成转录因子、肌生成素和肌细胞增强因子-2 （MEF2）的表达和活性。此外，Kir2.1目前先于肌生成素和MEF2的表达/活性的发育增加，并且是必需的。药物或反义降低Kir2.1电流减少或抑制融合以及肌生成素和MEF2的表达/活性。相比之下，LY294002，一种磷脂酰肌醇3-激酶（一种控制肌生成程序启动的途径）抑制剂，抑制肌生成素/MEF2的表达和融合，不影响Kir2.1电流。LY294002不阻断表明Kir2.1作用于myogenin和MEF2的上游。我们提出Kir2.1通道激活是一个必要的关键早期事件，通过超极化激活的Ca2+依赖途径，通过打开肌生成素和MEF2转录因子来启动肌肉发生。
It is widely thought that myogenin is one of the earliest detectable markers of skeletal muscle differentiation. Here we show that, during human myoblast differentiation, an inward rectifier K+ channel (Kir2.1) and its associated hyperpolarization trigger expression and activity of the myogenic transcription factors, myogenin and myocyte enhancer factor-2 (MEF2). Furthermore, Kir2.1 current precedes and is required for the developmental increase in expression/activity of myogenin and MEF2. Drugs or antisense reducing Kir2.1 current diminished or suppressed fusion as well as expression/ activity of myogenin and MEF2. In contrast, LY294002, an inhibitor of phosphatidylinositol 3-kinase ( a pathway controlling initiation of the myogenic program) that inhibited both myogenin/MEF2 expression and fusion, did not affect Kir2.1 current. This non-blockade by LY294002 indicates that Kir2.1 acts upstream of myogenin and MEF2. We propose that Kir2.1 channel activation is a required key early event that initiates myogenesis by turning on myogenin and MEF2 transcription factors via a hyperpolarization-activated Ca2+-dependent pathway.