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Slc4a8 in the Kidney: Expression, Subcellular Localization and Role in Acid Base Homeostasis and Salt Reabsorption
Author(s) -
Xu Jie,
Barone Sharon,
Zahedi Kamyar,
Brooks Marybeth,
Soleimani Manoocher
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.750.18
Subject(s) - kidney , homeostasis , epithelial polarity , chemistry , bicarbonate , intercalated cell , pendrin , microbiology and biotechnology , reabsorption , furosemide , medicine , endocrinology , biology , biochemistry , transporter , membrane , gene
Background The sodium‐dependent bicarbonate transporter Slc4a8 (a.k.a NDCBE) mediates the co‐transport of sodium and bicarbonate in exchange for chloride. It is abundantly detected in the brain, with low expression levels in the kidney. The cell distribution and subcellular localization of Slc4a8 in the kidney and its role in acid/base and electrolyte homeostasis has been the subject of conflicting reports. There are no conclusive localization or functional studies to pinpoint the location and demonstrate the function of Slc4a8 in the kidney. Methods Molecular techniques, including in situ hybridization and RT‐PCR, were performed on kidney sections and tagged epitopes were used to examine the membrane targeting of Slc4a8 in polarized kidney cells. Crispr/Cas9 was used to generate and examine Slc4a8 KO mice. Result In situ hybridization and Zonal distribution studies showed no expression for Slc4a8 (NDCBE) in the cortex or in cortical collecting ducts (CCD). Slc4a8 was predominantly detected in the outer and inner medullary collecting ducts (OMCD and IMCD), and was targeted to the basolateral membrane of osmotically tolerant MDCK cells when confocal microscopy images were acquired. Slc4a8 KO mice did not show any abnormal salt or bicarbonate wasting under baseline conditions or in response to bicarbonate loading, salt restriction or furosemide‐induced diuresis. Conclusions Slc4a8 (NDCBE) is absent in the CCD and is predominantly localized on the basolateral membrane of medullary collecting duct cells. Further, Slc4a8 deletion does not cause any acid base or electrolyte abnormality in pathophysiologic states such as furosemide‐induced salt wasting or salt restriction. We suggest that Slc4a8 is likely involved in intracellular pH and volume regulation in medullary collecting duct cells. Support or Funding Information Merit Review 5 I01 BX001000‐06 award from the Department of Veterans Affairs, and funds from the Center on Genetics of Transport and Epithelial Biology at the University of Cincinnati.