Faculty Collaboration Database

Essential role of Kir5.1 channels in renal salt handling and blood pressure control. JCI Insight 2017 Sep 21;2(18)

Date

09/22/2017

Pubmed ID

28931751

Pubmed Central ID

PMC5621918

DOI

10.1172/jci.insight.92331

Scopus ID

2-s2.0-85049388582 (requires institutional sign-in at Scopus site)   71 Citations

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.

Author List

Palygin O, Levchenko V, Ilatovskaya DV, Pavlov TS, Pochynyuk OM, Jacob HJ, Geurts AM, Hodges MR, Staruschenko A

Authors

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amiloride
Animals
Blood Pressure
Female
Furosemide
Hydrochlorothiazide
Kidney Tubules, Distal
Male
Mutation
Potassium Channels, Inwardly Rectifying
Rats
Rats, Inbred Dahl
Sodium Chloride
Sodium Chloride, Dietary