Intracellular pH regulates CFTR activity, which in turn controls the transport of salt and bicarbonate, according to findings in the Journal of Biological Chemistry.

A team of researchers have figured out how the protein that causes cystic fibrosis (CF) is controlled under normal circumstances and how it goes awry. They were able to determine how cystic fibrosis transmembrane conductance regulator (CFTR) controls the pH level of cells and effects salt transport across cells under normal conditions.

The study appears December 18 in the Journal of Biological Chemistry in a paper titled “Direct Sensing of Intracellular pH by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl- Channel.”

CF patients carry a defective gene that disables or destroys its protein product called CFTR. “CFTR itself is a small passageway with a gate, called an ion channel, found on the surface of cells lining ducts and tubes, where it acts as a pathway for the movement of chloride ions, one component of salt, and regulates the transport of bicarbonate, one part of soda,” explains Jeng-Haur Chen, a postdoctoral researcher at the University of Iowa Carver College of Medicine and the lead author.

By adjusting the transport of these molecules, CFTR regulates the acid-base balance of cells. While scientists have had evidence that CFTR regulates pH in cells, it had been unknown how it detected changes in pH and knew when to adjust its activity.

So, Dr. Chen set out to test his idea that CFTR activity is directly regulated by intracellular pH itself. He successfully demonstrated that acid pH potently stimulates chloride transport by CFTR, whereas alkali pH inhibits it.

Dr. Chen was also able to determine how pH regulates chloride transport via CFTR. He found that intracellular pH regulates ATP docking with the gate that controls access to the pathway through which chloride moves across the cell border. Intracellular pH also reportedly controls the speed at which this happens. Thus, intracellular pH determines the power level at the gate, which, in turn, regulates the transport of salt and bicarbonate, the scientists explain.

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