Figure 5.

ttna^Δ9/Δ9 adult zebrafish exhibit atrial fibrillation (AF), and both ttna^Δ9/Δ9 zebrafish atrial cardiomyocytes and TTN^Δ9/Δ9-hiPSC-aCMs demonstrate abnormal electrophysiology

(A) Representative electrocardiogram (ECG) recordings of 7–15-months-old ttna^+/+ (n = 20), ttna^Δ9/Δ9 (n = 17), and ttna^Δ9/Δ9 (n = 27) zebrafish hearts. Upper panel: ttna^+/+ ECG trace; middle panel: ttna^Δ9/+ ECG trace; lower panel: ttna^Δ9/Δ9 ECG trace demonstrating P-wave loss and arrhythmia.

(B) Quantification of AF incidence in ttna^+/+, ttna^Δ9/+, and ttna^Δ9/Δ9 adult zebrafish.

(C) Quantification of heartbeat interval standard deviation in zebrafish with AF in comparison to ttna^+/+ adults.

(D) Representative recordings of action potential (AP) on isolated ttna^+/+ (n = 5) and ttna^Δ9/Δ9 (n = 6) zebrafish atrial cardiomyocytes at 12 months of age.

(E) Quantification of AP duration at 90% repolarization (APD₉₀) in isolated zebrafish atrial cardiomyocytes.

(F) Representative optical AP recordings of TTN^+/+-hiPSC-aCMs and TTN^Δ9/Δ9-hiPSC-aCMs with voltage-sensitive dye VF2.1Cl.

(G) Quantification of APD₉₀ in hiPSC-aCMs (n = 4 independent batches, n = 5–6 biological replicates per batch). Data in (C, E, and G) are represented as mean ±95% confidence intervals. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. See also Figure S8.