Activation of Na:2Cl:K cotransport by luminal chloride in macula densa cells

Kidney International
Jean-Yves LapointePhillip Darwin Bell

Abstract

Changes in macula densa intracellular pH (pHi) were used to monitor the direction of flux mediated by the apical Na:2Cl:K cotransporter. At the macula densa, a decrease in luminal [Cl] ([Cl]1) from 60 to 1 mM produced cellular alkalinization secondary to a cascade of events involving a decrease in apical Na:2Cl:K cotransport, a fall in intracellular [Na] ([Na]i) and a stimulation of Na:H exchange. This is supported by the fact that 97% of the change in macula densa pHi with reduction in [Cl]1 was bumetanide-sensitive whereas 92% of this pH change was amiloride-sensitive. We found that, in the presence of 20 mM Na and 5 mM K, a [Cl]1 of 14.3 +/- 2.4 mM (N = 7) produced equilibrium of the apical cotransporter since the pHi obtained under this condition was identical to the pHi found after reducing the net ionic flux to zero with bumetanide. Using this value together with the expected stoichiometry for the bumetanide-sensitive cotransporter, it was estimated that the intracellular [Cl] ([Cl]i) at equilibrium (or in the presence of bumetanide) could be as low as 5 mM. Also, using a Hill number of 2 which is consistent with the present data, the affinity for [Cl]1 was found to be 32.5 mM. Under physiological luminal conditions preva...Continue Reading

References

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Citations

Mar 31, 2009·Purinergic Signalling·P Darwin BellZhi-Ren Zhang
Aug 22, 2000·Acta Physiologica Scandinavica·A E Persson, S Bachmann
Sep 15, 1998·Kidney International. Supplement·J Y LapointeP D Bell
Jul 1, 1997·Clinical and Experimental Pharmacology & Physiology·L Barajas
Jul 1, 1997·Clinical and Experimental Pharmacology & Physiology·P D Bell, J Y Lapointe
Jan 14, 2003·Annual Review of Physiology·P Darwin BellJános Peti-Peterdi
Aug 20, 2010·American Journal of Physiology. Renal Physiology·Arnold SiposJános Peti-Peterdi
Mar 1, 1995·Kidney International·B C FowlerP D Bell
Aug 5, 2004·American Journal of Physiology. Renal Physiology·Fabienne QuentinDominique Eladari
Dec 13, 2018·American Journal of Physiology. Renal Physiology·Joshua L Rein, Steven G Coca
Nov 14, 1998·The American Journal of Physiology·M A LaamartiJ Y Lapointe
Dec 31, 1997·The American Journal of Physiology·M A Laamarti, J Y Lapointe
Jun 13, 2001·American Journal of Physiology. Cell Physiology·O AharonovitzS Grinstein
Apr 24, 2003·American Journal of Physiology. Renal Physiology·Jean-Yves LapointeYasunobu Okada
Jan 5, 2000·Physiological Reviews·J M Russell
Mar 5, 1998·The American Journal of Physiology·J Schnermann
Sep 30, 2003·Journal of the American Society of Nephrology : JASN·Gergely KovácsP Darwin Bell
May 23, 2003·Journal of the American Society of Nephrology : JASN·Jurgen Schnermann

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