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Direct mechano-stress sensitivity of TRPM7 channel

机译：TRPM7通道的直接机械应力敏感性

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It has recently been shown that shear stress augments the heterologously expressed TRPM7 channel activity by exocytosis-mediated incorporation of TRPM7 into the plasma membrane. On the other hand, our recent study has shown that the TRPM7-like channel endogenously expressed in HeLa cells is activated by membrane expansion induced by membrane stretch or osmotic cell swelling. Thus, the present study was aimed at exploring the possibility that the heterogously expressed TRPM7 channel is activated directly by membrane expansion in a manner independent of exocytosis. Here, whole-cell currents of the TRPM7 channel heterologously expressed in HEK293T cells were found to be augmented not only by perfusion of bath solution but also by osmotic swelling even under the conditions where exocytotic events can hardly take place in the cytosol dialyzed with ATP-free, Ca2+- free and EGTA- containing pipette solution. In addition, shear stress- induced augmentation was not affected by a blocker of vesicular protein traffic, brefeldin A. Furthermore, in cell- free patches, membrane stretch directly augmented single- channel activity of TRPM7 by increasing Po value at <= 20mV. We thus conclude that the TRPM7 channel can be directly activated by mechano- stress in a manner independent of exocytosis- mediated incorporation of this channel protein into the plasma membrane. Copyright (c) 2007 S. Karger AG, Basel
机译：最近已经显示，剪应力通过胞吐作用介导的TRPM7掺入质膜而增强了异源表达的TRPM7通道活性。另一方面，我们最近的研究表明，HeLa细胞内源性表达的TRPM7样通道被膜拉伸或渗透性细胞溶胀诱导的膜膨胀激活。因此，本研究的目的是探讨杂合表达的TRPM7通道被膜扩张以不依赖胞吐作用的方式直接激活的可能性。在这里，发现在HEK293T细胞中异源表达的TRPM7通道的全细胞电流不仅通过浴液的灌注而增加，而且通过渗透溶胀而增加，即使在几乎不发生胞吐事件的条件下，用ATP-透析的胞质中也是如此。不含，不含Ca2 +和EGTA的移液器。此外，剪切应力诱导的增强不受囊泡蛋白运输的阻断剂布雷菲德菌素A的影响。此外，在无细胞膜片中，膜拉伸通过增加<= 20mV的Po值直接增加TRPM7的单通道活性。因此，我们得出这样的结论：机械应力可直接激活TRPM7通道，而与胞吐作用介导的将该通道蛋白并入质膜的方式无关。版权所有（c）2007 S.Karger AG，巴塞尔

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