Figure 6. Reduced sodium channel availability and decreased sodium current amplitude at the intercalated disc in CAR+/− cardiomyocytes.
(A) Action potentials (APs) measured from isolated left ventricular cardiomyocytes of WT and CAR+/− hearts (inset: dV/dt of the AP upstroke). (B) Average AP characteristics. Maximal AP upstroke velocity (dV/dtmax) was significantly lower in CAR+/− myocytes as compared to WT (* p<0.05). Resting membrane potential (RMP); action potential amplitude (APA) and action potential duration at 20, 50 and 90% of repolarization (APD20, APD50 and APD90, respectively) were not different between WT and CAR+/−. (C,D) Current-voltage (I-V) relationships show similar INa amplitude at the lateral membrane of WT and CAR+/− cardiomyocytes (C), but reduced INa amplitude in CAR+/− versus WT at the intercalated disc (assesed by two-way RM ANOVA followed by Holm-Sidak post-hoc testing: p=0.002 for overall effect) (D). Asterisks (*)denote membrane potentials at which INa amplitude is significantly different between WT and CAR+/−. (E,F) Average voltage-dependencies of activation and inactivation demonstrate no significant difference between WT and CAR+/− at the lateral membrane (E) or at the intercalated disc (ID) (F).
