Figure 3.

Reduced SERCA activity in the adjacent region. Representative recordings of Ca²⁺ transients are illustrated for cardiomyocytes during 1 Hz pacing, followed by rapid application of 10 mmol/L caffeine (A). The magnitude of caffeine-elicited Ca²⁺ release, an indicator of SR Ca²⁺ content, tended to be lower in the medial and distal regions (B). Fits of the declining phases of 1 Hz and caffeine transients revealed slowed SR Ca²⁺ reuptake in HFrEF cardiomyocytes from the adjacent region (C), while the rate of NCX Ca²⁺ extrusion tended to be higher in the remote zone (D) (n_hearts = 4, 5 in sham, HFrEF). (E) Caffeine transients recorded in the presence of 5 mmol/L Ni²⁺ revealed no alterations in Ca²⁺ fluxes via slow extrusion pathways (n_hearts = 2, 3 in sham, HFrEF). (F) Simulations of Ca²⁺ transients at physiological frequency (6 Hz) demonstrate the consequences of enhancing NCX activity (blue), as observed in myocytes from the distal zone, or reducing SERCA activity (red), as observed in the adjacent zone. *P < 0.05, calculated by nested ANOVA.