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Am J Physiol Renal Physiol 286: F1054-F1058, 2004. First published January 28, 2004; doi:10.1152/ajprenal.00336.2003
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Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake

Peter Komlosi,1,2 Janos Peti-Peterdi,1,2 Amanda L. Fuson,1 Attila Fintha,1,2 Laszlo Rosivall,2 and Phillip Darwin Bell1

1Division of Nephrology, Departments of Medicine and Physiology, University of Alabama at Birmingham, Birmingham, Alabama 35294; and 2Institute of Pathophysiology, Hungarian Academy of Sciences and Semmelweis University Nephrology Research Group, Budapest H-1089, Hungary

Submitted 22 September 2003 ; accepted in final form 19 January 2004

One component of the macula densa (MD) tubuloglomerular feedback (TGF) signaling pathway may involve basolateral release of ATP through a maxi-anion channel. Release of ATP has previously been studied during a maximal luminal NaCl concentration ([NaCl]L) stimulus (20–150 mmol/l). Whether MD ATP release occurs during changes in [NaCl]L within the physiological range (20–60 mmol/l) has not been examined. Also, because TGF is known to be enhanced by low dietary salt intake, we examined the pattern of MD ATP release from salt-restricted rabbits. Fluorescence microscopy, with fura 2-loaded cultured mouse mesangial cells as biosensors, was used to assess ATP release from the isolated, perfused thick ascending limb containing the MD segment. The mesangial biosensor cells, which contain purinergic receptors and elevate intracellular Ca2+ concentration ([Ca2+]i) on ATP binding, were placed adjacent to the MD basolateral membrane. Elevations in [NaCl]L between 0 and 80 mmol/l, in 20-mmol/l increments, caused stepwise increases in [Ca2+]i, with the highest increase at [NaCl]L of ~60 mmol/l. Luminal furosemide at 10–4 mol/l blocked ATP release, which suggests that the efflux of ATP required MD Na-2Cl-K cotransport. A low-salt diet for 1 wk increased the magnitude of [NaCl]L-dependent elevations in biosensor [Ca2+]i by twofold, whereas high-salt intake had no effect. In summary, ATP release occurs over the same range of [NaCl]L (20–60 mmol/l) previously reported for TGF responses, and, similar to TGF, ATP release was enhanced by dietary salt restriction. Thus these two findings are consistent with the role of MD ATP release as a signaling component of the TGF pathway.

tubuloglomerular feedback; fluorescent microscopy; salt diet; purinergic receptors


Address for reprint requests and other correspondence: P. Komlosi, 865 Sparks Center, 1720 Seventh Ave. South, Birmingham, AL 35294 (E-mail: pkomlosi{at}uab.edu).




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