Cloning and expression of the beta and gamma subunits of the human
epithelial sodium channel.
McDonald, Fiona J., Margaret P. Price, Peter M. Snyder, and Michael J. Welsh.
Howard Hughes Medical Institute, Departments of Internal Medicine,
Physiology and Biophysics, University of Iowa College of Medicine, Iowa City,
Iowa 52242, U.S.A.
APStracts 2:0057C, 1995.
Amiloride-sensitive Na+ channels are an important component of the Na+
reabsorption pathway in a number of epithelia. Here we report the cloning and
characterization of cDNAs encoding two subunits of the human kidney
epithelial Na+ channel ([beta] and gammahENaC). Their predicted amino acid
sequences were highly homologous (83-85% identical) to the corresponding
subunits reported from rat colon ([beta] and gammarENaC). Both [beta] and
gammahENaC mapped to human chromosome 16. Northern blot analysis showed high
expression of [beta] and gammahENaC in kidney and lung, and differential
expression of the three subunits in other tissues. Coexpression of [beta] and
gammahENaC with [alpha]hENaC in Xenopus oocytes produced Na+ channels with
high selectivity for Na+ and high sensitivity to amiloride. In addition, human
subunits were able to substitute for the corresponding rat subunits in forming
functional Na+ channels, suggesting conservation of function and suggesting
that differences in sequence do not disrupt interactions between subunits.
These results suggest that human [alpha], [beta], and gammaENaC together form
Na+ channels with properties that are similar to those observed in epithelia,
and will allow further investigation into the role that these channels may
play in human disease.
Received 8 November 1994; accepted in final form 20 December 1994.
APS Manuscript Number C661-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 27 February 1995.