» Articles » PMID: 37442855

KCNE1 Does Not Shift TMEM16A from a Ca Dependent to a Voltage Dependent Cl Channel and is Not Expressed in Renal Proximal Tubule

Overview
Journal Pflugers Arch
Specialty Physiology
Date 2023 Jul 13
PMID 37442855
Authors
Affiliations
Soon will be listed here.
Abstract

The TMEM16A (ANO1) Cl channel is activated by Ca in a voltage-dependent manner. It is broadly expressed and was shown to be also present in renal proximal tubule (RPT). KCNQ1 is an entirely different K selective channel that forms the cardiac I potassium channel together with its ß-subunit KCNE1. Surprisingly, KCNE1 has been claimed to interact with TMEM16A, and to be required for activation of TMEM16A in mouse RPT. Interaction with KCNE1 was reported to switch TMEM16A from a Ca2-dependent to a voltage-dependent ion channel. Here we demonstrate that KCNE1 is not expressed in mouse RPT. TMEM16A expressed in RPT is activated by angiotensin II and ATP in a KCNE1-independent manner. Coexpression of KCNE1 does not change TMEM16A to a voltage gated Cl channel and Ca-dependent regulation of TMEM16A is fully maintained in the presence of KCNE1. While overexpressed KCNE1 slightly affects Ca-dependent regulation of TMEM16A, the data provide no evidence for KCNE1 being an auxiliary functional subunit for TMEM16A.

Citing Articles

Identification of KCNE6, a new member of the KCNE family of potassium channel auxiliary subunits.

Kasuya G, Zempo B, Yamamoto Y, Ryu K, Ono F, Nakajo K Commun Biol. 2024; 7(1):1662.

PMID: 39702752 PMC: 11659587. DOI: 10.1038/s42003-024-07352-6.

References
1.
Attali B, Guillemare E, Lesage F, Honore E, Romey G, Lazdunski M . The protein IsK is a dual activator of K+ and Cl- channels. Nature. 1993; 365(6449):850-2. DOI: 10.1038/365850a0. View

2.
Avalos Prado P, Hafner S, Comoglio Y, Wdziekonski B, Duranton C, Attali B . KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies. Cell. 2020; 184(2):534-544.e11. DOI: 10.1016/j.cell.2020.11.047. View

3.
Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G . K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature. 1996; 384(6604):78-80. DOI: 10.1038/384078a0. View

4.
Barro-Soria R, Perez M, Larsson H . KCNE3 acts by promoting voltage sensor activation in KCNQ1. Proc Natl Acad Sci U S A. 2015; 112(52):E7286-92. PMC: 4703023. DOI: 10.1073/pnas.1516238112. View

5.
Buchholz B, Faria D, Schley G, Schreiber R, Eckardt K, Kunzelmann K . Anoctamin 1 induces calcium-activated chloride secretion and proliferation of renal cyst-forming epithelial cells. Kidney Int. 2013; 85(5):1058-67. DOI: 10.1038/ki.2013.418. View