The Brugada syndrome mutation A39V disrupts N-lobe CDI of Cav1.2 channels. A) Representative Ba2+ (black) and Ca2+ (red) traces of WT and A39V-Cav1.2 channels (B) expressed with Cavβ2a/Cavα2δ in the presence of low calcium buffering (0.5 mM EGTA) and CaM34. Note that the peak of the Ba2+ trace is normalized to that in the presence of Ca2+. For reference the WT-Cav1.2 Ca2+ trace is displayed in grey in (B). The plots shown below the current traces reflect average CDI (f300) which is quantified by the fraction of current remaining after 300 ms (r300) in calcium, and is then subtracted from the fraction of current remaining in barium at the same time point. The f300 value at 10 mV (arrows) is significantly less for A39V, than WT-Cav1.2 (# p ≤ 0.04 by student’s t-test). The inset bar graph displays additional f300 values over a potential range from -10 mV to +30 mV. A significant difference is observed in the f300 values between WT-Cav1.2 and A39V-Cav1.2 at −10, 0 and +10 mV (p ≤ 0.05 by student’s t-test), but not at +20 (p = 0.28 by student’s t-test) or +30 mV (p = 0.26 by student’s t-test). C) Under high calcium buffering (10 mM BAPTA) conditions WT-Cav1.2 channels expressed as in (A) no longer exhibit N-lobe CDI. D) A39V-Cav1.2 does not show significant N-lobe CDI compared to WT-Cav1.2 in high calcium buffering at +10 mV (arrows). For reference the WT-Cav1.2 Ca2+ trace (C) is displayed in grey.