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J. Biol. Chem., Vol. 277, Issue 11, 8767-8770, March 15, 2002
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From the Department of Cellular and Molecular Physiology, Yale
University School of Medicine, New Haven, Connecticut 06511
Three splice variants of the renal
Na-K-Cl cotransporter (NKCC2 F, A, and B) are spatially distributed
along the thick ascending limb of the mammalian kidney. To test
whether NKCC2 splice variants differ in ion transport characteristics
we expressed cDNAs encoding rabbit NKCC2 F, A, and B in
Xenopus oocytes and determined the ion dependence of
bumetanide-sensitive 86Rb influx. The three splice variants
of NKCC2 showed dramatic differences in their kinetic behavior. The
medullary variant F exhibited 3-4-fold lower affinity than variants A
and B for Na+ and K+. Chloride affinities also
markedly distinguish the three variants (KmF = 111.3, KmA = 44.7, and
KmB = 8.9 mM Cl
ACCELERATED PUBLICATION
Spatially Distributed Alternative Splice Variants of the Renal
Na-K-Cl Cotransporter Exhibit Dramatically Different Affinities for
the Transported Ions*
,
).
Thus, the kinetic properties of the NKCC2 splice variants are consistent with the spatial distribution of the variants along the
thick ascending limb as they are involved in reabsorbing
Na+, K+, and Cl from a
progressively diluted fluid in the tubule lumen. Variant B also showed
an anomalous inhibition of rubidium influx at high extracellular
Na+ concentrations, possibly important in its highly
specialized role in the macula densa. The adaptation of the kinetic
characteristics of the NKCC2 variants to the luminal concentrations of
substrate represents an excellent example of functional specialization
and diversity that can be achieved through alternative mRNA splicing.
*
This research was supported by National Institutes of Health
Grant DK-17433 and a fellowship (to I. G.) from the Ministerio de
Educación y Cultura of Spain.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Cellular and
Molecular Physiology, Yale University School of Medicine, 333 Cedar
St., New Haven, CT 06520-8026. Tel.: 203-7373-2586; Fax: 203-785-6834;
E-mail: ignacio.gimenez@yale.edu.
§
Present address: Groupe de Recherche en Nephrologie, Dept. of
Medicine, Faculty of Medicine, Laval University, Quebec G1R 2J6, Canada.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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