AE4 is a DIDS-sensitive Cl-/HCO3 - exchanger in the basolateral membrane of the renal CCD and the SMG duct

Shigeru B H Ko, Xiang Luo, Henrik Hager, Alexandra Rojek, Joo Young Choi, Christoph Licht, Makoto Suzuki, Shmuel Muallem, Søren Nielsen, Kenichi Ishibashi

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The renal cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. The β-intercalated cells secrete most of the HCO3 -, which is mediated by a luminal, DIDS-insensitive, Cl-/HCO3 - exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-PK1 cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (pHi) revealed that AE4 indeed functions as a Cl-/HCO3 - exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in α-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a Cl-/HCO3 - exchanger in the basolateral membrane of α-intercalated cells and may participate in HCO3 - absorption. In the rabbit AE4 may contribute to HCO3 - secretion.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number4 52-4
StatePublished - Oct 2002

Fingerprint

Chloride-Bicarbonate Antiporters
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Ducts
Anions
Protein Isoforms
Membranes
Kidney
Rats
Rabbits
Cell Membrane
LLC-PK1 Cells
RNA Isoforms
Acids
Cell membranes

Keywords

  • α-intercalated cells
  • 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid
  • Anion exchanger isoform 4
  • Cortical collecting duct
  • Kidney
  • Submandibular gland

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

AE4 is a DIDS-sensitive Cl-/HCO3 - exchanger in the basolateral membrane of the renal CCD and the SMG duct. / Ko, Shigeru B H; Luo, Xiang; Hager, Henrik; Rojek, Alexandra; Choi, Joo Young; Licht, Christoph; Suzuki, Makoto; Muallem, Shmuel; Nielsen, Søren; Ishibashi, Kenichi.

In: American Journal of Physiology - Cell Physiology, Vol. 283, No. 4 52-4, 10.2002.

Research output: Contribution to journalArticle

Ko, SBH, Luo, X, Hager, H, Rojek, A, Choi, JY, Licht, C, Suzuki, M, Muallem, S, Nielsen, S & Ishibashi, K 2002, 'AE4 is a DIDS-sensitive Cl-/HCO3 - exchanger in the basolateral membrane of the renal CCD and the SMG duct', American Journal of Physiology - Cell Physiology, vol. 283, no. 4 52-4.
Ko, Shigeru B H ; Luo, Xiang ; Hager, Henrik ; Rojek, Alexandra ; Choi, Joo Young ; Licht, Christoph ; Suzuki, Makoto ; Muallem, Shmuel ; Nielsen, Søren ; Ishibashi, Kenichi. / AE4 is a DIDS-sensitive Cl-/HCO3 - exchanger in the basolateral membrane of the renal CCD and the SMG duct. In: American Journal of Physiology - Cell Physiology. 2002 ; Vol. 283, No. 4 52-4.
@article{79c4d2a0bb8843458001bb6ae65dc4b0,
title = "AE4 is a DIDS-sensitive Cl-/HCO3 - exchanger in the basolateral membrane of the renal CCD and the SMG duct",
abstract = "The renal cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. The β-intercalated cells secrete most of the HCO3 -, which is mediated by a luminal, DIDS-insensitive, Cl-/HCO3 - exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-PK1 cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (pHi) revealed that AE4 indeed functions as a Cl-/HCO3 - exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in α-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a Cl-/HCO3 - exchanger in the basolateral membrane of α-intercalated cells and may participate in HCO3 - absorption. In the rabbit AE4 may contribute to HCO3 - secretion.",
keywords = "α-intercalated cells, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, Anion exchanger isoform 4, Cortical collecting duct, Kidney, Submandibular gland",
author = "Ko, {Shigeru B H} and Xiang Luo and Henrik Hager and Alexandra Rojek and Choi, {Joo Young} and Christoph Licht and Makoto Suzuki and Shmuel Muallem and S{\o}ren Nielsen and Kenichi Ishibashi",
year = "2002",
month = "10",
language = "English (US)",
volume = "283",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 52-4",

}

TY - JOUR

T1 - AE4 is a DIDS-sensitive Cl-/HCO3 - exchanger in the basolateral membrane of the renal CCD and the SMG duct

AU - Ko, Shigeru B H

AU - Luo, Xiang

AU - Hager, Henrik

AU - Rojek, Alexandra

AU - Choi, Joo Young

AU - Licht, Christoph

AU - Suzuki, Makoto

AU - Muallem, Shmuel

AU - Nielsen, Søren

AU - Ishibashi, Kenichi

PY - 2002/10

Y1 - 2002/10

N2 - The renal cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. The β-intercalated cells secrete most of the HCO3 -, which is mediated by a luminal, DIDS-insensitive, Cl-/HCO3 - exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-PK1 cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (pHi) revealed that AE4 indeed functions as a Cl-/HCO3 - exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in α-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a Cl-/HCO3 - exchanger in the basolateral membrane of α-intercalated cells and may participate in HCO3 - absorption. In the rabbit AE4 may contribute to HCO3 - secretion.

AB - The renal cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. The β-intercalated cells secrete most of the HCO3 -, which is mediated by a luminal, DIDS-insensitive, Cl-/HCO3 - exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-PK1 cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (pHi) revealed that AE4 indeed functions as a Cl-/HCO3 - exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in α-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a Cl-/HCO3 - exchanger in the basolateral membrane of α-intercalated cells and may participate in HCO3 - absorption. In the rabbit AE4 may contribute to HCO3 - secretion.

KW - α-intercalated cells

KW - 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid

KW - Anion exchanger isoform 4

KW - Cortical collecting duct

KW - Kidney

KW - Submandibular gland

UR - http://www.scopus.com/inward/record.url?scp=17644449375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17644449375&partnerID=8YFLogxK

M3 - Article

VL - 283

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 52-4

ER -