Direct Mechano-Stress Sensitivity of TRPM7 Channel

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Abstract
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.