Fig. 3: Dysfunctional GPCR-mediated inhibition in DDSA mutants.
From: Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea
a, Representative currents at +50 mV of WT TASK-1 channels (WT-WT) and ‘heterozygous’ channels from coexpressed WT and N133S subunits, over time while adding 10 µM carbachol. This concentration produces ~50% inhibition of WT TASK-1. b, Currents normalized to the initial WT current for WT TASK-1 coexpressed 1:1 with DDSA mutants before and after addition of 10 µM carbachol. WT TASK-1 (n = 6), L122V (n = 21), G129D (n = 19), N133S (n = 24), L239P (n = 18) and L241F (n = 26); data are presented as mean ± s.d. c,d, Equivalent recordings for WT TASK-1 coexpressed 1:1 with each DDSA mutant as indicated and the P2Y receptor (1:1:4). The current levels shown are before and after addition of 300 µM ATP normalized to the initial WT current. TASK-1 (n = 12), L122V (n = 13), G129D (n = 12), N133S (n = 12), L239P (n = 12) and L241F (n = 18); data are presented as mean ± s.d. The GPCR-mediated inhibition of mutant channel currents is reduced.
