HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 12, 9668-9675, March 22, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/12/9668    most recent M110852200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sangan, P. Articles by Binder, H. J. Search for Related Content PubMed PubMed Citation Articles by Sangan, P. Articles by Binder, H. J. Social Bookmarking                      What's this?

Cloning and Expression of a Chloride-dependent Na⁺-H⁺ Exchanger^*

Pitchai Sangan, Vazhaikkurichi M. Rajendran, John P. Geibel^§¶, and Henry J. Binder^§

From the  Departments of Internal Medicine, ^§ Cellular and Molecular Physiology, and ^¶ Surgery, Yale University, New Haven, Connecticut 06520-8019

Electroneutral Na⁺-H⁺ exchange is present in virtually all cells, mediating the exchange of extracellular Na⁺ for intracellular H⁺ and, thus, plays an important role in the regulation of intracellular pH, cell volume, and transepithelial Na⁺ absorption. Recent transport studies demonstrated the presence of a novel chloride-dependent Na⁺-H⁺ exchange in the apical membrane of crypt cells of rat distal colon. We describe the cloning of a 2.5-kb full-length cDNA from rat distal colon that encodes 438 amino acids and has six putative transmembrane spanning domains. Of the 438 amino acids 375 amino acids at the N-terminal region are identical to Na⁺-H⁺ exchange (NHE)-1 isoform with the remaining 63 amino acids comprising a completely novel C terminus. In situ hybridization revealed that this transcript is expressed in colonic crypt cells, whereas Northern blot analysis established the presence of its 2.5-kb mRNA in multiple tissues. Despite its much smaller size compared with all other known Na⁺-H⁺ exchange isoforms, NHE-deficient PS120 fibroblasts stably transfected with this cDNA exhibited Na⁺-dependent intracellular pH recovery to an acid load that was chloride-dependent and inhibited both by 5-ethylisopropylamiloride, an amiloride analogue, and by 5'-nitro-2-(3-phenylproplyamino)benzoic acid, a Cl channel blocker, but only minimally affected by 25 µM 3-methylsulfonyl-4piperidonbenzoylguanidine, an NHE-1 and NHE-2 isoform inhibitor. In contrast to other Na⁺-H⁺ exchange isoforms in colonic epithelial cells, chloride-dependent Na⁺-H⁺ exchange mRNA abundance was increased by dietary sodium depletion. Based on these results we predict that chloride-dependent Na⁺-H⁺ exchange represents a new class of Na⁺-H⁺ exchangers that may regulate ion transport in several organs.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF462063.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. N. Orlov and A. A. Mongin Salt-sensing mechanisms in blood pressure regulation and hypertension Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2039 - H2053. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				S. M. Sidani, P. Kirchhoff, T. Socrates, L. Stelter, E. Ferreira, C. Caputo, K. E. Roberts, R. L. Bell, M. E. Egan, and J. P. Geibel {Delta}F508 Mutation Results in Impaired Gastric Acid Secretion J. Biol. Chem., March 2, 2007; 282(9): 6068 - 6074. [Abstract] [Full Text] [PDF]

				B. Etschmann, K. S. Heipertz, A. von der Schulenburg, and M. Schweigel A vH+-ATPase is present in cultured sheep ruminal epithelial cells Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1171 - G1179. [Abstract] [Full Text] [PDF]

				O. Bachmann, B. Riederer, H. Rossmann, S. Groos, P. J. Schultheis, G. E. Shull, M. Gregor, M. P. Manns, and U. Seidler The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G125 - G133. [Abstract] [Full Text] [PDF]

				V. Faundez and H. C. Hartzell Intracellular Chloride Channels: Determinants of Function in the Endosomal Pathway Sci. Signal., May 18, 2004; 2004(233): re8 - re8. [Abstract] [Full Text] [PDF]

				G. Laverty, C. McWilliams, A. Sheldon, and S. S. Arnason PTH stimulates a Cl--dependent and EIPA-sensitive current in chick proximal tubule cells in culture Am J Physiol Renal Physiol, May 1, 2003; 284(5): F987 - F995. [Abstract] [Full Text] [PDF]