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Subunit of ENaC
1 Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA
2 Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: deaton{at}emory.edu.
One of the defining characteristics of ENaC is its block by the diuretic amiloride. This study investigates the role of the extracellular loop of the 
ENaC subunit in amiloride binding and stabilization. Mutations were generated in a region of the extracellular loop, residues 278-283. Deletion of this region, WYRFHY, resulted in a loss of amiloride binding to the channel. Channels formed from either wild type subunits or subunits containing point mutations in this region were examined and compared at the single channel level. The open probabilities (Po) of wild type channels were distributed into two populations, one with a high Po and one with a low Po. The mean open times (
open) of all the mutants were shorter than the open of the wild type (high Po) channel. Besides mutations Y279A and H282D that had similar amiloride binding affinities to that of wild type ENaC , all other mutations in this region caused changes in the amiloride binding affinity of the channels compared to wild type. These data provide new insight into the relative position of the extracellular loop with respect to the pore of ENaC and its role in amiloride binding and channel gating.
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