Functional coupling of ion channels in cellular mechanotransduction |
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Authors: | Vladislav I Chubinskiy-Nadezhdin Yuri A Negulyaev Elena A Morachevskaya |
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Institution: | 1. Institute of Cytology RAS, St. Petersburg, Russia;2. Department of Medical Physics, St. Petersburg State Polytechnical University, St. Petersburg, Russia |
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Abstract: | The major players in the processes of cellular mechanotransduction are considered to be mechanosensitive (MS) or mechano-gated ion channels. Non-selective Ca2+-permeable channels, whose activity is directly controlled by membrane stretch (stretch-activated channels, SACs) are ubiquitously present in mammalian cells of different origin. Ca2+ entry mediated by SACs presumably has a significant impact on various Ca2+-dependent intracellular and membrane processes. It was proposed that SACs could play a crucial role in the different cellular reactions and pathologies, including oncotransformation, increased metastatic activity and invasion of malignant cells. In the present work, coupling of ion channels in transformed fibroblasts in course of stretch activation was explored with the use of patch-clamp technique. The combination of cell-attached and inside-out single-current experiments showed that Ca2+ influx via SACs triggered the activity of Ca2+-sensitive K+ channels indicating functional compartmentalization of different channel types in plasma membrane. Importantly, the analysis of single channel behavior demonstrated that K+ currents could be activated by the rise of intracellular calcium but displayed no direct mechanosensitivity. Taken together, our data imply that local changes in Ca2+ concentration due to SAC activity may provide a functional link between various Ca2+-dependent molecules in the processes of cellular mechanotransduction. |
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Keywords: | Mechanotransduction Stretch-activated channels Calcium signaling Transformed fibroblasts |
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