Sodium–calcium exchanger 1 is the key molecule for urinary potassium excretion against acute hyperkalemia

Autor: Tatemitsu Rai, Takahiro Iwamoto, Shinichi Uchida, Hideaki Tagashira, Koichiro Susa, Kiyoshi Isobe, Eisei Sohara, Wakana Shoda, Naohiro Nomura, Akihito Ohta, Takayasu Mori, Fumiaki Ando
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Physiology
Immunofluorescence
030204 cardiovascular system & hematology
Biochemistry
Mice
0302 clinical medicine
Mathematical and Statistical Techniques
Medicine and Health Sciences
Small interfering RNAs
Post-Translational Modification
Phosphorylation
Kidney Tubules
Distal
Multidisciplinary
Aniline Compounds
biology
Chemistry
Phenyl Ethers
Statistics
Sodium/Calcium Exchanger 1
Nucleic acids
medicine.anatomical_structure
Research Design
embryonic structures
Physical Sciences
Medicine
Anatomy
Intracellular
Research Article
Calmodulin
Science
Sodium
Immunoblotting
Excretion
chemistry.chemical_element
Molecular Probe Techniques
Research and Analysis Methods
Sodium-Calcium Exchanger
Dephosphorylation
03 medical and health sciences
parasitic diseases
medicine
Genetics
Animals
Humans
Distal convoluted tubule
Statistical Methods
Non-coding RNA
Molecular Biology Techniques
Immunoassays
Molecular Biology
Analysis of Variance
urogenital system
Quantitative Analysis
Biology and Life Sciences
Proteins
Kidneys
Renal System
Molecular biology
Gene regulation
030104 developmental biology
HEK293 Cells
biology.protein
Immunologic Techniques
Potassium
RNA
Hyperkalemia
Gene expression
Cotransporter
Physiological Processes
Mathematics
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 6, p e0235360 (2020)
ISSN: 1932-6203
Popis: The sodium (Na+)-chloride cotransporter (NCC) expressed in the distal convoluted tubule (DCT) is a key molecule regulating urinary Na+ and potassium (K+) excretion. We previously reported that high-K+ load rapidly dephosphorylated NCC and promoted urinary K+ excretion in mouse kidneys. This effect was inhibited by calcineurin (CaN) and calmodulin inhibitors. However, the detailed mechanism through which high-K+ signal results in CaN activation remains unknown. We used Flp-In NCC HEK293 cells and mice to evaluate NCC phosphorylation. We analyzed intracellular Ca2+ concentration ([Ca2+]in) using live cell Ca2+ imaging in HEK293 cells. We confirmed that high-K+-induced NCC dephosphorylation was not observed without CaN using Flp-In NCC HEK29 cells. Extracellular Ca2+ reduction with a Ca2+ chelator inhibited high-K+-induced increase in [Ca2+]in and NCC dephosphorylation. We focused on Na+/Ca2+ exchanger (NCX) 1, a bidirectional regulator of cytosolic Ca2+ expressed in DCT. We identified that NCX1 suppression with a specific inhibitor (SEA0400) or siRNA knockdown inhibited K+-induced increase in [Ca2+]in and NCC dephosphorylation. In a mouse study, SEA0400 treatment inhibited K+-induced NCC dephosphorylation. SEA0400 reduced urinary K+ excretion and induced hyperkalemia. Here, we identified NCX1 as a key molecule in urinary K+ excretion promoted by CaN activation and NCC dephosphorylation in response to K+ load.
Databáze: OpenAIRE
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