| Literature DB >> 28931751 |
Oleg Palygin1,2, Vladislav Levchenko1, Daria V Ilatovskaya1, Tengis S Pavlov1, Oleh M Pochynyuk3, Howard J Jacob1,4, Aron M Geurts1,4,5, Matthew R Hodges1,2, Alexander Staruschenko1,5.
Abstract
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.Entities:
Keywords: Epithelial transport of ions and water; Ion channels; Nephrology; Potassium channels
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Year: 2017 PMID： 28931751 PMCID： PMC5621918 DOI： 10.1172/jci.insight.92331
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708