Regulation of transient receptor potential canonical channel 1 (TRPC1) by sphingosine 1-phosphate in C2C12 myoblasts and its relevance for a role of mechanotransduction in skeletal muscle differentiation
Regulation of transient receptor potential canonical channel 1 (TRPC1) by sphingosine 1-phosphate in C2C12 myoblasts and its relevance for a role of mechanotransduction in skeletal muscle differentiation
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DOI：
10.1242/jcs.035402
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Meacci, Elisabetta
中科院分区：
文献类型：
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作者：
Formigli, Lucia;Sassoli, Chiara;Meacci, Elisabetta
瞬时受体电位通道提供阳离子和钙离子进入途径，在包括肌肉营养不良在内的许多生理病理过程中起着重要的调节作用。然而，这些通道的激活机制仍然知之甚少。利用siRNA，我们首次提供了实验证据，证明TRPC通道1(TRPC1)除了作为存储操作的通道外，还代表了C2C12骨骼肌母细胞拉伸激活通道的重要组成部分，通过全细胞膜片钳和原子力显微镜拉力进行了分析。神经鞘氨醇1-磷酸(S1P)是一种参与卫星细胞生物学和组织再生的生物活性脂质，它调节通道的活动和牵张诱导的钙内流。我们还发现TRPC1在脂筏中进行了功能性组装，这一事实表明胆固醇耗竭导致跨膜离子电流和电导降低。联谊会
Transient receptor potential canonical (TRPC) channels provide cation and Ca2+ entry pathways, which have important regulatory roles in many physio-pathological processes, including muscle dystrophy. However, the mechanisms of activation of these channels remain poorly understood. Using siRNA, we provide the first experimental evidence that TRPC channel 1 (TRPC1), besides acting as a store-operated channel, represents an essential component of stretch-activated channels in C2C12 skeletal myoblasts, as assayed by whole-cell patch-clamp and atomic force microscopic pulling. The channel's activity and stretch-induced Ca2+ influx were modulated by sphingosine 1-phosphate (S1P), a bioactive lipid involved in satellite cell biology and tissue regeneration. We also found that TRPC1 was functionally assembled in lipid rafts, as shown by the fact that cholesterol depletion resulted in the reduction of transmembrane ion current and conductance. Association