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 |
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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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