RGD Reference Report - Essential role of Kir5.1 channels in renal salt handling and blood pressure control. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Essential role of Kir5.1 channels in renal salt handling and blood pressure control.

Authors: Palygin, Oleg  Levchenko, Vladislav  Ilatovskaya, Daria V  Pavlov, Tengis S  Pochynyuk, Oleh M  Jacob, Howard J  Geurts, Aron M  Hodges, Matthew R  Staruschenko, Alexander 
Citation: Palygin O, etal., JCI Insight. 2017 Sep 21;2(18). pii: 92331. doi: 10.1172/jci.insight.92331. eCollection 2017 Sep 21.
RGD ID: 38500204
Pubmed: PMID:28931751   (View Abstract at PubMed)
PMCID: PMC5621918   (View Article at PubMed Central)
DOI: DOI:10.1172/jci.insight.92331   (Journal Full-text)

Supplementing diets with high potassium helps reduce hypertension in humans. Inwardly rectifying K+ channels Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16) are highly expressed in the basolateral membrane of distal renal tubules and contribute to Na+ reabsorption and K+ secretion through the direct control of transepithelial voltage. To define the importance of Kir5.1 in blood pressure control under conditions of salt-induced hypertension, we generated a Kcnj16 knockout in Dahl salt-sensitive (SS) rats (SSKcnj16-/-). SSKcnj16-/- rats exhibited hypokalemia and reduced blood pressure, and when fed a high-salt diet (4% NaCl), experienced 100% mortality within a few days triggered by salt wasting and severe hypokalemia. Electrophysiological recordings of basolateral K+ channels in the collecting ducts isolated from SSKcnj16-/- rats revealed activity of only homomeric Kir4.1 channels. Kir4.1 expression was upregulated in SSKcnj16-/- rats, but the protein was predominantly localized in the cytosol in SSKcnj16-/- rats. Benzamil, but not hydrochlorothiazide or furosemide, rescued this phenotype from mortality on a high-salt diet. Supplementation of high-salt diet with increased potassium (2% KCl) prevented mortality in SSKcnj16-/- rats and prevented or mitigated hypertension in SSKcnj16-/- or control SS rats, respectively. Our results demonstrate that Kir5.1 channels are key regulators of renal salt handling in SS hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension treatmentIAGPcontrolled sodium content diet and controlled potassium content diet38500204compared to SS-Kcnj16em1McwiRGD 
hypokalemia  ISOKcnj16 (Rattus norvegicus)38500204; 38500204protein:decreased expression:cortical collecting duct and distal convoluted tubule (rat)RGD 
hypokalemia  IMP 38500204protein:decreased expression:cortical collecting duct and distal convoluted tubule (rat)RGD 
hypokalemia  IMP 38500204; 38500204compared to SS/JrHsdMcwiRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
basolateral plasma membrane  IDA 38500204MMO:0000538RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased body weight  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
decreased circulating aldosterone level  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
decreased heart rate  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
decreased renal glomerular filtration rate  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
decreased systemic arterial blood pressure  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
decreased urine microalbumin level  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
hypokalemia  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
increased blood urea nitrogen level  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
increased circulating magnesium level  IMP 38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
increased susceptibility to induced morbidity/mortality treatmentIMPcontrolled sodium content diet and Benzamil38500204; 38500204; 38500204compared to SS/JrHsdMcwiRGD 
renal cast  IAGP 38500204compared to SS-Kcnj16em1McwiRGD 
salt-sensitive hypertension treatmentIAGPcontrolled sodium content diet and controlled potassium content diet38500204compared to SS-Kcnj16em1McwiRGD 
Objects Annotated

Genes (Rattus norvegicus)
Kcnj16  (potassium inwardly-rectifying channel, subfamily J, member 16)
Kcnj16em1Mcwi  (potassium inwardly-rectifying channel, subfamily J, member 16; zinc finger nuclease induced mutant 1, Medical College of Wisconsin)

Genes (Mus musculus)
Kcnj16  (potassium inwardly-rectifying channel, subfamily J, member 16)

Genes (Homo sapiens)
KCNJ16  (potassium inwardly rectifying channel subfamily J member 16)

Strains
SS-Kcnj16em1Mcwi-/-  (NA)
SS/JrHsdMcwi  (NA)


Additional Information