Figure 8. Pharmacological stimulation of I _Ca (L‐type Ca current) using Bay K8644 restores Ca transients in AngII (angiotensin II)‐treated knock‐in (KI) myocytes and rescues left ventricular dysfunction in failing KI mice following transverse aortic constriction (TAC).

A, Original traces (A) of intracellular Ca transients measured in Fura‐2 loaded ventricular myocytes from wild‐type (WT) (upper panel) and KI mice (lower panel) in the absence (left) and presence of 1 µmol/L Bay K8644 (right). F₃₄₀/F₃₈₀ indicates the fluorescence intensity ratio measured with Fura‐2. Although Ca transients were significantly reduced in KI cells upon sole AngII treatment (left), addition of Bay K8644 induced a significant increase in Ca transient amplitude in both groups that was significantly more pronounced in KI cells (right). Average data for (A) are depicted in (B). Data are normally distributed (Shapiro‐Wilk test). *Indicates significance vs AngII control using 2‐way (TW) ANOVA with Holm‐Sidak post‐test. C, Original M‐mode traces of WT (upper panel) and KI mice (lower panel) after TAC and following acute stimulation of I _Ca using Bay K8644. Average data in (D) demonstrate a significantly enhanced inotropic response in KI mice following acute stimulation of I _Ca using Bay K8644. Data are normally distributed (D'Agostino‐Pearson test). ^#Indicates significance vs WT using unpaired t test. LVEF indicates left ventricular ejection fraction.