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This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007080900v1 19/10/1940    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Komlosi, P. Articles by Bell, P. D. PubMed PubMed Citation Articles by Komlosi, P. Articles by Bell, P. D.

Oscillating Cortical Thick Ascending Limb Cells at the Juxtaglomerular Apparatus

Peter Komlosi^*, Boglarka Banizs, Attila Fintha, Stacy Steele^*, Zhi-Ren Zhang^* and P. Darwin Bell^*

^* Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina; and Department of Cell Biology and Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama

Correspondence: Dr. Peter Komlosi, 173 Ashley Avenue, CRI 211, P.O. Box 250623, Charleston, SC 29425. Phone: 843-792-5350; Fax: 843-792-5521; E-mail: komlosi{at}musc.edu

Received for publication August 15, 2007. Accepted for publication April 30, 2008.

While studying the intracellular calcium dynamics in cells of the macula densa, the observation was made that tubular epithelial cells located near the macula densa and associated with the renal arterioles exhibit spontaneous Ca²⁺ oscillations. In this study, the cortical thick ascending limb–distal tubule, with attached glomerulus, was isolated and perfused. At a low luminal sodium chloride concentration, Ca²⁺ oscillations at a frequency of 63 mHz were observed in tubular cells that were within 100 µm of the macula densa plaque using four-dimensional multiphoton microscopy and wide-field fluorescence microscopy with fura-2. The Ca²⁺ oscillations were absent in the macula densa cells. Spontaneous oscillations in basolateral membrane potential suggested that Ca²⁺ oscillations occurred, at least in part, through depolarization-induced increases in Ca²⁺ entry. The amplitude of these Ca²⁺ oscillations was significantly enhanced by the activation of the Ca²⁺-sensing receptor. Increasing the luminal sodium chloride concentration or luminal flow resulted in a significant increase in both the amplitude of Ca²⁺ oscillations and the intracellular Ca²⁺ concentration in perimacular cortical thick ascending limb cells. In addition, luminal furosemide attenuated the [NaCl]_L-dependent changes in intracellular Ca²⁺ concentration, but hydrochlorothiazide had no effect. These findings demonstrate that tubular epithelial cells at the perimeter of the macula densa exhibit spontaneous oscillations in intracellular Ca²⁺ concentration, enhanced by tubular flow and luminal sodium chloride. These oscillatory patterns may play a role in juxtaglomerular signaling.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673