Mechanical Forces in the Kidney
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The renal tubules of the kidney function to reabsorb water, ions, and organic molecules from the filtrate destined to become urine. As it passes through the sections of the tubule, the majority of the fluid and electrolytes are transported back into the plasma, leaving the waste products behind, which pass on to the collecting duct system, the urethra, and out of the body. Importantly, the quantity of fluid flowing through the tubule can vary greatly—up to ten-fold-yet the total amount of reabsorption is remarkably stable. How the tubule senses such dramatic changes in flow has been a "mystery for about 4 decades now," says bioengineer Sheldon Weinbaum of the City College of New York.
Each endothelial cell in the first section of the renal tubules is lined with thousands of densely packed protrusions known as microvilli. For years, scientists believed that the function...
Indeed, a 2003 study found that changes in torque applied to the microvilli by fluid flow corresponded almost perfectly with changes in electrolyte reabsorption, which drives water reabsorption in the tubule (PNAS 101:13068-73, 2003). Furthermore, the microvilli are "almost uniform in height," Weinbaum says, which is critical for their collective behavior in sensing fluid flow. "If their whole function is just for transport, then it wouldn't matter that it looked like someone went with a lawnmower and cut them all the same height."
Alternatively, scientists have suspected that primary cilia of the tubule also sense fluid flow. These cilia, which extend like microvilli, are much less frequent—with only one per cell at most—and are a bit longer, protruding slightly above "the forest of the microvilli," Weinbaum says. The cilia, which are essentially extensions of the internal cytoskeleton, sense fluid flow in the cortical collecting duct (CCD)—the last section of the renal tubule, where microvilli are absent. As the filtrate flows through the CCD, the cilia bend, initiating conformational changes of proteins located at the base of the cilia that together function as mechanosensitive calcium channels.
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