Which of the following statements best explains how this deletion will affect the CFTR protein?

When CFTR is defective other channels, including the outwardly rectifying chloride channel (ORCC), the epithelial sodium channel (ENaC), a potassium channel known as ROMK1 and a chloride/bicarbonate exchanger, do not work properly. In addition, other chloride channels present on the surface of epithelial cells may be affected in the CF airways. These “alternative” chloride channels have been proposed as a therapeutic target to enhance chloride transport.

The ORCC is found on the surface of many epithelial cells. Normal CFTR facilitates the transport of adenosine triphosphate (ATP), an energy-carrying molecule, to the outside of the cell, activating ORCC. It is unknown whether CFTR itself or an associated channel actually transports the ATP. However, the mutant CFTR is not able to perform the function of transporting ATP.

The ENaC, a sodium channel found on the surface of epithelial cells, is made up of four subunits: two alpha, one beta and one gamma. Each subunit consists of two transmembrane helices. CFTR also influences the function of ENaC in the lung by decreasing its activity, however, the mechanism by which this occurs is unclear.

As suggested by its name, the chloride/bicarbonate exchanger transports one bicarbonate molecule out the cell for every chloride that it transports into the cell. The chloride is derived from the efflux of chloride through CFTR. Therefore, if CFTR is not functional the activity of this channel will be greatly reduced.

Several other chloride channels are present on the cell surface. The one that may be most influenced by CFTR is the CaCC or calcium-activated chloride channel. The exact protein that creates this channel has yet to be defined. However, it is known that the channel is modulated by the P2Y2 receptor which is activated by ATP. Therefore, the activity of this channel could be influenced by decreased ATP associated with mutant CFTR..

CFTR regulates the function of other ion channels located within the cell membrane.

*Reference is also in this collection.

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Summary of CFTR coding regions according to historical and current nomenclature