Stretch-activated ion channels.

Mechanosensitive or stretch-activated (SA) channels respond to membrane stress by changes in open probability. These channels exist in auditory cells, stretch receptors, muscle spindles, vascular endothelium, and other neurosensory tissues where their physiological function seems readily apparent. It is less obvious why non-excitable cells, such as those of blood and epithelial tissues, need channels that respond to mechanical stimuli. Clearly, all cells must cope with the dual problems of volume regulation and electrolyte homeostasis. Since the primary function of epithelia is salt and water transport, these cells face both extracellular and intracellular osmotic challenges. For example, Na transporting epithelia in the intestine and kidney must accommodate significant variations in net solute uptake without suffering destructive changes in cell volume, caused by slight discrepancies between influx and efflux [1]. Since volume is a physical property of the cell, it can only be sensed physically, or mechanically. Although cell swelling may dilute the concentration of certain impermeants that could conceivably function as intracellular volume sensors, a volume-controller that relies on chemical sensors is inherently unstable because chemical concentration is affected by multiple factors within the cell. A reliable feedback system for short-term volume regulation ultimately requires some type of mechanical sensor to convey information about cell size. Similarly, regulation of cell growth may also require specific mechanotransducers that detect physical changes in cell size and shape. Conversely, the abnormal growth of cancer cells could involve a breakdown of such a mechano-transduction system.