ESDR102 - Loss of volume-regulated anion channel LRRC8 interferes with cell volume regulation and epidermal homeostasis

Molecular identification was, at last, successfully accomplished for three types of anion channels that are all implicated in cell volume regulation/dysregulation. LRRC8A plus LRRC8C/D/E, SLCO2A1, and TMEM206 were shown to be the core or pore-forming molecules of the volume-sensitive outwardly rectifying anion channel (VSOR) also called the volume-regulated anion channel (VRAC), the large-conductance maxi-anion channel (Maxi-Cl), and the acid-sensitive outwardly rectifying anion channel (ASOR) also called the proton-activated anion channel (PAC) in 2014, 2017, and 2019, respectively. More recently in 2020 and 2021, we have identified the S100A10-annexin A2 complex and TRPM7 as the regulatory proteins for Maxi-Cl and VSOR/VRAC, respectively. In this review article, we summarize their biophysical and structural properties as well as their physiological roles by comparing with each other on the basis of their molecular insights. We also point out unsolved important issues to be elucidated soon in the future.

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Tannins, novel inhibitors of the volume regulation and the volume-sensitive anion channel

European Pharmaceutical Journal ◽

10.2478/afpuc-2019-0016 ◽

2019 ◽

Vol 66 (2) ◽

pp. 37-44 ◽

Cited By ~ 1

Author(s):

N.A. Tsiferova ◽

O. J. Khamidova ◽

A. U. Amonov ◽

M. B. Rakhimova ◽

S. I. Rustamova ◽

...

Keyword(s):

Cell Volume ◽

Volume Regulation ◽

Cell Volume Regulation ◽

Anion Channel ◽

Regulation System ◽

Hydrolysable Tannins ◽

Rhus Typhina ◽

Higher Doses ◽

Specific Membrane ◽

Hct116 Cells

Abstract The volume-sensitive outwardly rectifying anion channel (VSOR) is a key component of volume regulation system critical for cell survival in non-isosmotic conditions. The aim of the present study was to test the effects of four tannin extracts with defined compositions on cell volume regulation and VSOR. Preparation I (98% of hydrolysable tannins isolated from leaves of sumac Rhus typhina L.) and Preparation II (100% of hydrolysable tannins isolated from leaves of broadleaf plantain Plantago major L) completely and irreversibly abolished swelling-activated VSOR currents in HCT116 cells. Both preparations profoundly suppressed the volume regulation in thymocytes with half-maximal effects of 40.9 μg/ml and 12.3 μg/ml, respectively. The inhibition was more efficient at lower concentrations but reverted at higher doses due to possible non-specific membrane-permeabilizing activity. Preparations III and IV (54,7% and 54.3% of hydrolysable tannins isolated, respectively, from roots and aboveground parts of Fergana spurge Euphorbia ferganensis B.Fedtch) inhibited VSOR activity in a partially reversible manner and suppressed the volume regulation with substantially higher half-maximal doses of 270 and 278 μg/ml, respectively, with no secondary reversion at higher doses. Hydrolysable tannins represent a novel class of VSOR channel inhibitors with the capacity to suppress the cell volume regulation machinery.

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