NYMC Faculty Publications

Kir5.1 Regulates Kir4.2 Expression and Is a Key Component of the 50-Ps Inwardly Rectifying Potassium Channel in Basolateral Membrane of Mouse Proximal Tubules

Author Type(s)

Faculty

DOI

10.1152/ajprenal.00178.2024

Journal Title

American Journal of Physiology Renal Physiology

First Page

F248

Last Page

F257

Document Type

Article

Publication Date

2-1-2025

Department

Pharmacology

Keywords

Kcnj10, Kcnj15, Kcnj16, potassium channel, proximal tubule

Disciplines

Medicine and Health Sciences

Abstract

Kir5.1 encoded by Kcnj16 is an inwardly rectifying Kþ channel subunit, and it possibly interacts with Kir4.2 subunit encoded by Kcnj15 for assembling a Kir4.2/Kir5.1 heterotetramer in the basolateral membrane of mouse proximal tubule.We now used patch clamp technique to examine basolateral Kþ channels of mouse proximal tubule (PT) and an immunoblotting/immunofluorescence (IF) staining microscope to examine Kir4.2 expression in wild-type and Kir5.1-knockout mice.IF staining shows that Kir4.2 was exclusively expressed in the proximal tubule, whereas Kir5.1 was expressed in the proximal tubule and distal nephrons including distal convoluted tubule.Immunoblotting showed that the expression of Kir4.2 monomer was lower in Kir5.1-knockout mice than that in the wild-type mice.In contrast, Kir4.1 monomer expression was increased in Kir5.1 knockout mice.IF images further demonstrated that the basolateral membrane staining of Kir4.2 was significantly decreased in Kir5.1 knockout mice.This is in sharp contrast to Kir4.1, which also interacts with Kir5.1 in the distal nephron, and IF images show that Kir4.1 membrane expression was still visible and unchanged in Kir5.1 knockout mice.The single channel recording detected a 50-pS inwardly rectifying Kþ channel, presumably a Kir4.2/Kir5.1 heterotetramer, in the basolateral membrane of the proximal tubule of Kir5.1 wild-type mice.However, this 50-pS Kþ channel was completely absent in the basolateral membrane of the proximal tubule of Kir5.1 knockout mice.Moreover, the membrane potential of the proximal tubule was less negative in Kir5.1 knockout mice than wild-type mice.We conclude that Kir5.1 is essential for assembling basolateral 50-pS Kþ channel in proximal tubule and that deletion of Kir5.1 decreased Kir4.2 expression in the proximal tubule thereby decreasing the basolateral Kþ conductance and the membrane potentials.

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