Fig. 2.

Fig. 2.

Impact of the Gβ5-S81L variant on I_K,ACh in RA-treated hiPSC-CMs. (A,B) Typical recordings (A) and average I_K,ACh density (B) in WT, S81L^het and S81L^homo hiPSC-CMs. Average I_K,ACh density is increased in S81L^homo hiPSC-CMs compared to WT and S81L^het hiPSC-CMs. *P<0.05 (Kruskal–Wallis non-parametric test, followed by Bonferroni post-hoc analysis). (C,D) Time constant (τ) of I_K,ACh activation (C) and deactivation (D). (B-D) WT, n=27; S81L^het, n=11; S81L^homo, n=20 hiPSC-CMs. (E) Percentage of desensitization, measured as the percentage of I_K,ACh decrease at steady state upon continuous CCh application; WT, n=3; S81L^het, n=6; S81L^homo, n=5 hiPSC-CMs. (F) Transcript level of the genes involved in G-protein-coupled activation of I_K,ACh. Data are mean±s.e.m. of three biological differentiation replicas and expression level of each gene in S81L^het and S81L^homo hiPSC-CMs is indicated as relative to its expression in WT hiPSC-CMs. No significant differences are observed in KCNJ3, KCNJ5, RGS6 and GNB5 transcript abundance across the WT, S81L^het and S81L^homo hiPSC-CMs.