Kidney Week

Abstract: FR-OR030

Deletion of Voltage-Gated K+ Channel 7.1 (Kv7.1) in Interculated Cells (ICs) Causes Metabolic Acidosis and Hypokalemia

Session Information

• Electrolyte and Acid-Base Homeostasis: New Insights
  October 23, 2026 | Location: Room 405, Convention Center
  Abstract Time: 04:50 PM - 05:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Author

• Wang, Wen-Hui, New York Medical College School of Medicine, Valhalla, New York, United States

Wen-Hui Wang, MD

Background

Kv7.1 encoded by Kcnq1 is expressed in the heart, pacreatic β-cell and kidney. Patients with lost-of-function mutations of Kcnq1 have a long-QT-syndrom and valnerable for having type-II diabetics. RNA-seq study of the mouse kidney demonstrated that Kcnq1 mRNA is expressed in A-IC and B-IC.The aim of the study is to determine the location and function of Kv7.1 in the kidney.

Methods

We have generated inducible kidney-tubule-specific Kcnq1 conditional knockout (Ks-Kcnq1-KO) mice and IC-specific Kcnq1-KO mice for the study. We used the patch-clamp technique to determine Kv7.1 activity, used immunoblotting and IF to examine the expression of AE1 and pendrin, and used metabolic cage to study the baseline kidney function.

Results

Whole-cell-recordings detect chromonol-293b (a specific Kv7.1-inhibitor)-sensitive K⁺ currents in cells which have no Ba²⁺-sensitive inwardly-rectifying K⁺ currents (Kir). In contrast, chromanol-293b had no effect on K⁺ currents of principal-cells which have Ba²⁺-sensitive Kir currents, The notion that Kv7.1 are present in ICs is also confirmed by IF showing KV7.1 is expressed in AQP2-negative cells. IF images also demonstrate that Kv7.1 is expressed in the basolateral-membrane in pendrin-positive B-IC and colocalized with AE1 in A-IC. Single-channel-recording ( cell-attached) detects a 5-6-pS K⁺ channel during depolarization in the basolateral- membrane of ICs. This K⁺ channel is completely absent in A-IC and B-IC of Kv7.1-KO mice. Both Ks-Kv7.1-KO and IC-Kv7.1-KO mice have similar phenotypes under control conditions, including increased urinary volume, alkalized urine, increased urinary Na⁺ and K⁺ excretion in comparison to wild-type (WT) mice. Kv7.1-KO mice are hypokalemic and metabolic acidosis in comparison to WTmice. The expression of pendrin and AE1 is lower in Kv7.1-KO mice than WT mice. Allso, ICs of Kv7.1-KO mice have lower basolateral membrane potential and smaller NPPB-sensitive Cl^- currents than WT mice.

Conclusion

Kv7.1 K⁺ channel is expressed in the basolateral-membra of A-IC and B-IC, and it facilitates Cl exits across the basolateral-membrane by increasing negativity of the basolateral- membrane-potential. Deletion of Kv7.1 in ICs affects the expression/function of AE1 and pendrin thereby compromising renal K⁺ metabolism and acid-base balance.

Funding

• NIDDK Support