Figure 3. Fhf2^KO hearts have increased sensitivity to reduced gap junctional conductance.

(A,B) In vivo experiments with reduced gap junctional conductance using carbenoxolone or by mating into a cardiomyocyte-specific Cx43 heterozygous (Cx43 cHet) background. (A) Representative surface ECG tracings of Fhf2^WT, Cx43 cHet, Fhf2^KO, and Fhf2^KO;Cx43 cHet mice subjected to carbenoxolone. (B) QRS duration plotted against varying doses of carbenoxolone (60mg/kg, 90mg/kg, and 120mg/kg) via intraperitoneal (IP) injection and observed over 30 minutes (n=5 mice per cohort). (C) Representative epicardial left and right ventricular activation maps. Multiple regions of conduction block were observed in Fhf2^KO; Cx43 cHet hearts during epicardial pacing. Hearts were paced at 100 milliseconds basic cycle length. Isochrones are drawn 5 milliseconds apart (n=5 mice per cohort). (D) Quantification of left and right ventricular epicardial conduction velocity. Multiple regions of block precluded quantitative epicardial CV measurements in Fhf2^KO; Cx43 cHet hearts. Data represent median ± interquartile range. *significant p values < 0.05, Wilcoxon signed-rank test was performed for comparisons between paired samples; Mann–Whitney U-test used for comparison of independent variables; Kruskal-Wallis test for more than two groups followed by Benjamin-Hochberg post-hoc test for pairwise comparisons. See Online Table VIII for individual p-values.