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Physiological aspects of renal K+:Cl− cotransporters (KCCs) regulation
Author(s) -
MELO ZESERGIO CARLO,
Vazquez Norma,
Gamba Gerardo,
Mercado Adriana
Publication year - 2012
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.26.1_supplement.867.32
Subject(s) - endocrinology , dephosphorylation , medicine , cotransporter , xenopus , chemistry , acidosis , metabolic acidosis , diabetes mellitus , biology , phosphorylation , biochemistry , gene , sodium , phosphatase , organic chemistry
Little is known about the role of KCCs in renal physiology. KCCs are inactive in isotonic conditions and become active in hypotonicity, associated with dephosphorylation of the cotransporters in threonines residues 991 and 1048 of KCC3. Using Xenopus laevis oocytes we evaluated the functional properties of wild type KCC3 or KCC4 (WT) and double mutants KCC3 or KCC4 T991A/T1048A (TA2). In contrast to WT, the mutants TA2 exhibits constitutive activity under isotonic conditions. However, similar to WT, TA2s were further activated by hypotonicity and this activation was prevented by WNK3. In addition, the catalytically inactive WNK3 that activates WT in isotonicity also further increases the activity of TA2. These data suggest that besides T991/T1048 additional dephosphorylation sites are required for full activation of KCC3 or KCC4 by hypotonicity. On the other hand, we assessed the expression of KCC3 and KCC4 at the protein level in Wistar rat models of metabolic acidosis or streptozotocin‐induced diabetes mellitus. KCC4 expression is increased by metabolic acidosis in renal medulla, while KCC3 expression is increased during diabetes mellitus in renal cortex. These observations support a role for KCC4 in acid secretion by intercalated cells in which its expression has been confirmed, and for KCC3 in the response of proximal tubule cells to an increase in glucose concentration in the ultrafiltrate.