Role of CFTR and ClC-5 in Modulating Vacuolar H+-ATPase Activity in Kidney Proximal Tubule

Role of CFTR and ClC-5 in Modulating Vacuolar H+-ATPase Activity in Kidney Proximal Tubule

Author Carraro-Lacroix, Luciene Regina Autor UNIFESP Google Scholar
Lessa, Lucilia M. A. Google Scholar
Bezerra, Camila N. A. Google Scholar
Pessoa, Thaissa D. Google Scholar
Souza-Menezes, Jackson Google Scholar
Morales, Marcelo M. Google Scholar
Girardi, Adriana C. C. Google Scholar
Malnic, Gerhard Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Rio de Janeiro (UFRJ)
Abstract Background/Aims: It has been widely accepted that chloride ions moving along chloride channels act to dissipate the electrical gradient established by the electrogenic transport of H+ ions performed by H+-ATPase into subcellular vesicles. Largely known in intracellular compartments, this mechanism is also important at the plasma membrane of cells from various tissues, including kidney. the present work was performed to study the modulation of plasma membrane H+-ATPase by chloride channels, in particular, CFTR and ClC-5 in kidney proximal tubule. Methods and Results: Using in vivo stationary microperfusion, it was observed that ATPase-mediated HCO3- reabsorption was significantly reduced in the presence of the Cl- channels inhibitor NPPB. This effect was confirmed in vitro by measuring the cell pH recovery rates after a NH4Cl pulse in immortalized rat renal proximal tubule cells, IRPTC. in these cells, even after abolishing the membrane potential with valinomycin, ATPase activity was seen to be still dependent on Cl-. siRNA-mediated CFTR channels and ClC-5 chloride-proton exchanger knockdown significantly reduced H+-ATPase activity and V-ATPase B2 subunit expression. Conclusion: These results indicate a role of chloride in modulating plasma membrane H+-ATPase activity in proximal tubule and suggest that both CFTR and ClC-5 modulate ATPase activity. Copyright (C) 2010 S. Karger AG, Basel
Keywords H+-ATPase
Proximal tubule
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 04/01683-5
FAPESP: 05/60491-1
FAPESP: 06/50828-1
FAPESP: 07/52945-8
FAPESP: 09/51772-8
CNPq: 304855/2006-5
Date 2010-01-01
Published in Cellular Physiology and Biochemistry. Basel: Karger, v. 26, n. 4-5, p. 563-576, 2010.
ISSN 1015-8987 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 563-576
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000283859000008

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