Fig. 5: LRRC8A:D VRACs are gated open upon removal of pore lipids.
From: Assembly and lipid-gating of LRRC8A:D volume-regulated anion channels
a Focused side-view slice of the LRRC8A:D model pore with selectivity filter residues (white), pore lipids (salmon), and residue T48 (yellow) highlighted. b Whole-cell voltage-clamp recordings from LRRC8A-E–/– HeLa cells expressing wild-type (WT) LRRC8A:D (top), LRRC8A:D(T48D) (center-top), LRRC8A(T48D):D (center-bottom), or LRRC8A(T48D):D(T48D) (bottom) mutant channels. For each construct, representative current traces from isotonic (left) and hypotonic (center) solutions are displayed alongside corresponding plots of the current-voltage relationships (right; isotonic, green; hypotonic, blue). For current traces, 0 pA/pF is marked with a dotted line. c Fold-activation of WT and mutant LRRC8A:D channels following hypotonic swelling (Ihypotonic, 60 mV/Iisotonic, 60 mV). Data are displayed as the mean ± s.e.m. plotted alongside individual data points for WT LRRC8A:D (n = 9), LRRC8A:D(T48D) (n = 7), LRRC8A(T48D):D (n = 11), and LRRC8A(T48D):D(T48D) (n = 7). Differences were assessed using a Brown-Forsythe and Welch one-way ANOVA test followed by a Dunnett’s T3 multiple comparisons test to WT LRRC8A:D (n.s., not significant; **P = 0.0050 and P = 0.0032 for LRRC8A(T48D):D and LRRC8A(T48D):D(T48D), respectively) and a two-tailed unpaired t test comparing LRRC8A(T48D):D to LRRC8A(T48D):D(T48D) (*P = 0.0326).
