Tweety-homolog (Ttyh) Family Encodes the Pore-forming Subunits of the Swelling-dependent Volume-regulated Anion Channel (VRAC_swell) in the Brain.

ABSTRACT: In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl^-- and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC_swell) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRAC_swell in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl^- conductance (I_Cl,swell) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells,

SUBMITTER: Han YE 

PROVIDER: S-EPMC6526117 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature