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The ability of cells to convert mechanical perturbations into biochemical information is an essential aspect of mammalian physiology. The molecules that mediate such mechanotransduction include mechanically activated ion channels, which directly convert mechanical inputs into electrochemical signals. The unifying feature of these channels is that their open probability increases with the application of a mechanical input. However, the structure, activation profile and sensitivity of distinct mechanically activated ion channels vary from channel to channel. In this review, we discuss how ionic currents can be mechanically evoked and monitored in vitro, and describe the distinct activation profiles displayed by a range of mammalian channels. In addition, we discuss the various mechanisms by which the best-characterized mammalian, mechanically activated ion channel, PIEZO1, can be modulated. The diversity of activation and modulation of these mammalian ion channels suggest that these molecules may facilitate a finely controlled and diverse ability to sense mechanical inputs in mammalian cells.