Distinct cell types along thick ascending limb express pathways for monovalent and divalent cation transport
Hasan Demirci1,2,3, Jessica P Bahena-Lopez4, Alina Smorodchenko5
1Institute of Functional Anatomy and.
JCI Insight
|June 5, 2025
Summary
Researchers identified three distinct kidney thick ascending limb (TAL) cell types in rats, mice, and humans. These cell types differ in potassium channel and claudin expression, impacting ion reabsorption and urinary concentration.
Area of Science:
- Nephrology
- Cell Biology
- Physiology
Background:
- Kidney thick ascending limb (TAL) cells are crucial for reabsorbing sodium, potassium, calcium, and magnesium, contributing to urinary concentration.
- Traditionally viewed as a single cell type, recent transcriptomic data suggest heterogeneity within TAL cells, but a consensus model is lacking.
Purpose of the Study:
- To identify and classify distinct TAL cell types in rats, mice, and humans.
- To understand the functional implications of TAL cell diversity in kidney physiology and disease.
Main Methods:
- Immunolocalization
- Electrophysiology
- Enriched single-nucleus RNA-Sequencing (snRNA-Seq)
Main Results:
- Identification of three major TAL cell types based on differential expression of potassium channels and claudins.
- Characterization of cell types by apical/basolateral potassium conductance and claudin composition (monovalent vs. divalent cation permeability).
- Demonstration of conserved TAL cell types across species (rat, mouse, human).
Conclusions:
- The kidney TAL segment comprises at least three distinct cell types with specialized functions.
- Recognition of TAL cell diversity offers insights into selective solute transport modulation and mechanisms of kidney diseases.
- This classification provides a new framework for understanding TAL cell function and pathophysiology.
Keywords:
Calcium signalingEpithelial transport of ions and waterMetabolismNephrologyPotassium channelsMore Related Videos
11:51Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters
Published on: February 3, 2018
7.1K
06:59A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines
Published on: June 22, 2022
2.3K
Related Concept Videos
01:17Reabsorption and Secretion in the Loop of Henle
1.8K
The thick ascending limb of the nephron loop has Na+–K+–2Cl− symporters in the apical membranes of its cells. These symporters simultaneously reclaim one sodium ion, one potassium ion, and two chloride ions from the tubular fluid. Sodium ions are actively transported into the interstitial fluid at the base and sides of the cell, diffusing into the vasa recta. Chloride ions move through leakage channels in the basolateral membrane into the interstitial fluid and then into the...
1.8K
01:26Reabsorption and Secretion in the DCT and Collecting Duct
1.6K
The early phase of the DCT manages the reabsorption of approximately 10-15% of filtered water, 5–10% of filtered sodium, and 5–10% of filtered chloride. This process is facilitated by Na+–Cl− symporters in apical membranes and sodium-potassium pumps, as well as Cl− leakage channels in basolateral membranes. The early DCT also stands out as a site where parathyroid hormone (PTH) stimulates calcium reabsorption, depending on the body's requirements.
The distal...
The distal...
1.6K
01:22Physiology of the Genitourinary System II: Tubular Reabsorption and Secretion
113
The kidneys maintain homeostasis through filtration, reabsorption, and secretion. Tubular reabsorption and secretion are crucial in forming urine and regulating electrolytes, water balance, and waste elimination.Tubular Reabsorption and Secretion ProcessesTubular reabsorption is the process that reclaims essential substances such as electrolytes, glucose, amino acids, and water from the glomerular filtrate back into the bloodstream. This is achieved through passive and active transport...
113
01:23Transcellular Transport of Solutes
3.9K
Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
3.9K
01:31Membrane Transporters
13.1K
Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
13.1K
01:28Reabsorption and Secretion in the PCT
1.8K
The Proximal Convoluted Tubule, or PCT, plays a pivotal role in the body's filtration system. They are primarily responsible for reabsorbing solutes and water from the filtered fluid produced by the glomeruli. Most of the filtered water, ions, and organic solutes such as glucose and amino acids are reabsorbed by the PCT.
Transport mechanisms involving sodium ions (Na+) contribute significantly to solute reabsorption. These mechanisms include symport and antiport processes.
A key example is the...
Transport mechanisms involving sodium ions (Na+) contribute significantly to solute reabsorption. These mechanisms include symport and antiport processes.
A key example is the...
1.8K