Heterologous expression of rat nhe-4: a highly amiloride-resistant
na+/h+ exchanger isoform.
Chambrey, R[umlaut]agine, Jean-Michel Achard, and David G. Warnock.
Departments of Medicine and Physiology & Biophysics and
Nephrology Research and Training Center, University of Alabama at
Birmingham, UAB Station, Birmingham, Alabama 35294-0007 and
Department of Veterans Affairs Medical Center, Birmingham, AL
35233
APStracts 3:0234C, 1996.
Molecular cloning and expression have previously defined three members
of the Na+/H+ exchanger (NHE) gene family. NHE-1 and NHE-2 are
sensitive to inhibition by amiloride and its 5'-amino alkyl
substituted analogues, while NHE-3 is quite resistant to amiloride
inhibition. Each of these exchangers have narrowly defined cation
specificities for Na+ and Li+. Expression studies with NHE-4 have not
been as successful, with only a description of modest expression of
activity (Bookstein, et al. J. Biol. Chem. 269:29704-29709). We now
report that NHE-4 activity in stably transfected fibroblasts is
activated by 4,4'-di-isiothiocyanatostilbene-2,2'-disulfonic acid
(DIDS), permitting functional characterization of this NHE isoform.
The activating effect of DIDS was unique among the disulfonic
stilbenes, and competition studies suggested a cross-linking
mechanism. NHE-4 is extremely resistant to amiloride and ethyl
isopropyl amiloride inhibition, and unlike other NHE isoforms,
effects K+/H+ exchange as well as Na+/H+ and Li+/H+ exchange. These
findings demonstrate that NHE-4 is a functionally distinct member of
the NHE gene family and suggest a unique physiologic role for this
cation/H+ exchanger.
Received 18 January 1996; accepted in final form 10 July 1996
APS Manuscript Number C750-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996