Fig. 5: Knockout of Scn10a (NaV1.8) in CaMKIIδc+/T mice (SCN10A−/−/CaMKIIδc+/T) significantly reduces INaL and proarrhythmic triggers.
a Original traces of INaL in WT, SCN10A−/−, CaMKIIδc+/T, and SCN10A−/−/CaMKIIδc+/T mouse ventricular cardiomyocytes elicited using the protocol shown in the inset. b Mean data ± SEM along with individual values shown in the graph plotting (WT: n = 7 cells/4 mice, SCN10A−/− n = 10 cells/5 mice, CaMKIIδc+/T: n = 9 cells/5 mice; SCN10A−/−/CaMKIIδc+/T: n = 4 cells/4 mice), there was a significantly reduced INaL in SCN10A−/−/CaMKIIδc+/T cardiomyocytes compared to CaMKIIδc+/T. Data were analyzed by one-way ANOVA with post hoc Bonferroni’s correction. c Original traces of action potentials showing triggered action potentials originating from delayed afterdepolarizations (DADs) in CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T cardiomyocytes. d Graph of mean data ± SEM along with individual values showing DADs per minute in WT (n = 10 cells/5 mice), SCN10A−/− (n = 12 cells/5 mice), CaMKIIδc+/T (n = 21 cells/5 mice) and SCN10A−/−/CaMKIIδc+/T (n = 15 cells/5 mice) cardiomyocytes. There were significantly less events of afterdepolarizations in SCN10A−/−/CaMKIIδc+/T compared to CaMKIIδc+/T cardiomyocytes. Data were analyzed by one-way ANOVA with the post hoc two-stage step-up method of Benjamini, Krieger, and Yekutieli. e Original traces of action potential showing early afterdepolarizations (EADs) in CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T cardiomyocytes. f Graph of mean data ± SEM along with individual values showing EADs per minute in WT (n = 10 cells/5 mice), SCN10A−/− (n = 12 cells/5 mice), CaMKIIδc+/T (n = 21 cells/5 mice) and SCN10A−/−/CaMKIIδc+/T (n = 16 cells/5 mice) cardiomyocytes. There were significantly less events of afterdepolarizations in SCN10A−/−/CaMKIIδc+/T compared to CaMKIIδc+/T cardiomyocytes. Data were analyzed by one-way ANOVA with the post hoc two-stage step-up method of Benjamini, Krieger, and Yekutieli. g Original confocal line scans images of CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T cardiomyocytes showing diastolic Ca2+ waves. h Percentage of cells exhibiting waves was significantly less in SCN10A−/−/CaMKIIδc+/T (n = 74 cells/7 mice) compared to CaMKIIδc+/T (n = 104 cells/9 mice). Data were analyzed by Chi-square test, two-tailed analysis. i Significantly decreased number of Ca2+ waves per minute in SCN10A−/−/CaMKIIδc+/T compared to CaMKIIδc+/T. Data were analyzed by one-way ANOVA with post hoc Bonferroni’s correction. Cells/mice studied, WT: n = 48 cells/5 mice, SCN10A−/−: n = 52 cells/5 mice, CaMKIIδc+/T: n = 104 cells/9 mice; SCN10A−/−/CaMKIIδc+/T: n = 74 cells/7 mice. Data were presented as mean values ± SEM.
