Top ▲

Volume regulated chloride channels (VRAC) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

Click here for help

« Hide

Volume activated chloride channels (also termed VSOAC, volume-sensitive organic osmolyte/anion channel; VRC, volume regulated channel and VSOR, volume expansion-sensing outwardly rectifying anion channel) participate in regulatory volume decrease (RVD) in response to cell swelling. VRAC may also be important for several other processes including the regulation of membrane excitability, transcellular Cl- transport, angiogenesis, cell proliferation, necrosis, apoptosis, glutamate release from astrocytes, insulin (INS, P01308) release from pancreatic β cells and resistance to the anti-cancer drug, cisplatin (reviewed by [1-4]). VRAC may not be a single entity, but may instead represent a number of different channels that are expressed to a variable extent in different tissues and are differentially activated by cell swelling. In addition to ClC-3 expression products (see above) several former VRAC candidates including MDR1 (ABCB1 P-glycoprotein), Icln, Band 3 anion exchanger and phospholemman are also no longer considered likely to fulfil this function (see reviews [3,5]).

Channels and Subunits

710
Click here for help

VRAC C Show summary »


Target Id 710
Nomenclature VRAC
Previous and unofficial names VRAC (volume regulated anion channel) | VRC (volume regulated channel) | VSOAC (volume-sensitive organic osmolyte/anion channel) | VSOR (volume expansion-sensing outwardly rectifying anion channel)
Activators
GTPγS
Endogenous channel blockers
intracellular Mg2+
arachidonic acid
Channel blockers
tamoxifen
quinidine
quinine
mibefradil
1,9-dideoxyforskolin
9-anthroic acid
carbenoxolone
clomiphene
DCPIB
diBA-(5)-C4
DIDS
gossypol
IAA-94
mefloquine
nafoxidine
nordihydroguiaretic acid
NPPB
NS3728
Functional characteristics γ = 10-20 pS (negative potentials), 50-90 pS (positive potentials); permeability sequence SCN > I > NO3- >Br- > Cl- > F- > gluconate; outward rectification due to voltage dependence of γ; inactivates at positive potentials in many, but not all, cell types; time dependent inactivation at positive potentials; intracellular ionic strength modulates sensitivity to cell swelling and rate of channel activation; rate of swelling-induced activation is modulated by intracellular ATP concentration; ATP dependence is independent of hydrolysis and modulated by rate of cell swelling; inhibited by increased intracellular free Mg2+ concentration; swelling induced activation of several intracellular signalling cascades may be permissive of, but not essential to, the activation of VRAC including: the Rho-Rho kinase-MLCK; Ras-Raf-MEK-ERK; PIK3-NOX-H2O2 and Src-PLCγ-Ca2+ pathways; regulation by PKCα required for optimal activity; cholesterol depletion enhances activity; activated by direct stretch of β1-integrin
Comment VRAC is also activated by cell swelling and low intracellular ionic strength. VRAC is also blocked by chromones, extracellular nucleotides and nucleoside analogues

Comments

Click here for help

Show »

References

Click here for help

Show »

How to cite this family page

Database page citation:

Volume regulated chloride channels (VRAC). Accessed on 23/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=132.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie A, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. Br J Pharmacol. 176 Issue S1: S142-228.