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Am J Physiol Renal Physiol. 2015 Apr 15;308(8):F839-47. doi: 10.1152/ajprenal.00601.2014. Epub 2015 Jan 28.

Regulation of glomerulotubular balance. III. Implication of cytosolic calcium in flow-dependent proximal tubule transport.

Author information

1
Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut;
2
Department of Biomedical Engineering, City College of New York, CUNY, New York, New York; and.
3
Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York.
4
Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut; tong.wang@yale.edu.

Abstract

In the proximal tubule, axial flow (drag on brush-border microvilli) stimulates Na(+) and HCO3 (-) reabsorption by modulating both Na/H exchanger 3 (NHE3) and H-ATPase activity, a process critical to glomerulotubular balance. We have also demonstrated that blocking the angiotensin II receptor decreases baseline transport, but preserves the flow effect; dopamine leaves baseline fluxes intact, but abrogates the flow effect. In the current work, we provide evidence implicating cytosolic calcium in flow-dependent transport. Mouse proximal tubules were microperfused in vitro at perfusion rates of 5 and 20 nl/min, and reabsorption of fluid (Jv) and HCO3 (-) (JHCO3) were measured. We examined the effect of high luminal Ca(2+) (5 mM), 0 mM Ca(2+), the Ca(2+) chelator BAPTA-AM, the inositol 1,4,5-trisphosphate (IP3) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB), and the Ca-ATPase inhibitor thapsigargin. In control tubules, increasing perfusion rate from 5 to 20 nl/min increased Jv by 62% and JHCO3 by 104%. With respect to Na(+) reabsorption, high luminal Ca(2+) decreased transport at low flow, but preserved the flow-induced increase; low luminal Ca(2+) had little impact; both BAPTA and 2-APB had no effect on baseline flux, but abrogated the flow effect; thapsigargin decreased baseline flow, leaving the flow effect intact. With respect to HCO3 (-) reabsorption, high luminal Ca(2+) decreased transport at low flow and mildly diminished the flow-induced increase; low luminal Ca(2+) had little impact; both BAPTA and 2-APB had no effect on baseline flux, but abrogated the flow effect. These data implicate IP3 receptor-mediated intracellular Ca(2+) signaling as a critical step in transduction of microvillous drag to modulate Na(+) and HCO3 (-) transport.

KEYWORDS:

IP3 receptor; calcium signals; extracellular Ca2+; flow-dependent; sodium bicarbonate; tubule transport

PMID:
25651568
PMCID:
PMC4398834
DOI:
10.1152/ajprenal.00601.2014
[Indexed for MEDLINE]
Free PMC Article
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