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

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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.

Disease Annotations    
hypertension  (IAGP)
hypokalemia  (IMP,ISO)

Gene Ontology Annotations    

Cellular Component

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)

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

Additional Information