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Oscillating cortical thick ascending limb cells at the juxtaglomerular apparatus
Peter Komlosi1, Boglarka Banizs, Attila Fintha
1Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina, USA. komlosi@musc.edu
Insights
Tubular epithelial cells near the macula densa show spontaneous calcium (Ca2+) oscillations. These oscillations are influenced by sodium chloride concentration and tubular flow, suggesting a role in kidney function.
Area of Science:
- Nephrology
- Cell Physiology
- Renal Physiology
Background:
- Intracellular calcium (Ca2+) dynamics are crucial for cellular function.
- The macula densa plays a key role in regulating glomerular filtration rate and renal blood flow.
- Little is known about calcium signaling in tubular epithelial cells surrounding the macula densa.
Purpose of the Study:
- To investigate spontaneous intracellular Ca2+ oscillations in tubular epithelial cells near the macula densa.
- To determine the factors influencing these Ca2+ oscillations, including luminal sodium chloride concentration and flow.
- To explore the potential role of these oscillations in juxtaglomerular signaling.
Main Methods:
- Isolation and perfusion of the cortical thick ascending limb-distal tubule with attached glomerulus.
- Utilized four-dimensional multiphoton microscopy and wide-field fluorescence microscopy with fura-2.
- Measured intracellular Ca2+ concentration and basolateral membrane potential.
Main Results:
- Spontaneous Ca2+ oscillations (63 mHz) were observed in tubular cells within 100 microm of the macula densa at low luminal sodium chloride.
- Ca2+ oscillations were absent in macula densa cells.
- Oscillation amplitude increased with activation of the Ca2+-sensing receptor.
- Increased luminal sodium chloride concentration and flow enhanced Ca2+ oscillation amplitude and intracellular Ca2+ concentration.
- Furosemide attenuated sodium chloride-dependent changes, while hydrochlorothiazide had no effect.
Conclusions:
- Tubular epithelial cells at the macula densa perimeter exhibit spontaneous intracellular Ca2+ oscillations.
- These oscillations are enhanced by tubular flow and luminal sodium chloride concentration.
- The findings suggest a potential role for these oscillatory patterns in juxtaglomerular signaling and kidney regulation.
Abstract:
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 microm 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.
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