Fig. 2.

Direct electrophysiological effects of dapagliflozin on human atrial cardiomyocytes (CMs). a Left: Experimental protocol: fresh atrial tissue samples were obtained from N = 14 patients undergoing open heart surgery. APs from n = 34 isolated CMs were recorded at baseline and after administration of dapagliflozin at various concentrations (1, 10, 100 µmol/L), using current clamp measurements in a whole-cell configuration with ruptured patches. The scalebar in the lower panel indicates 25 µm. Right: Representative AP recordings, obtained from a human atrial CM at baseline and after administration of dapagliflozin (100 µmol/L). b AP inducibility (percentage of pulses evoking an AP, out of 10 current pulses elicited at a rate of 0.5 Hz; n/N = 15–28/5–13) and AP amplitude (APA) of elicited APs (n/N = 14–19/5–12) at baseline and 5 min after application of dapagliflozin (1, 10, 100 µmol/L). c Maximum upstroke velocity, AP duration at 50% and 90% repolarization (APD₅₀, APD₉₀) and resting membrane potential (RMP) in human atrial CMs under baseline conditions and 5 min after application of dapagliflozin (1, 10, 100 µmol/L; n/N = 14–19/5–12; stimulation frequency = 0.5 Hz). d Upper: Experimental protocol: human induced pluripotent stem cells (hiPSC) were differentiated in atrial- or ventricular-like hiPSC-derived CM (hiPSC-CM) and seeded on multi-electrode array (MEA) plates. Spontaneous field potentials were recorded under control conditions and after application of dapagliflozin at various concentrations (1, 10, 30, 100 µmol/L) or the vehicle. Lower: Representative field potential recordings, for atrial-and ventricular-like hiPSC-CM monolayers at baseline and 15 min after administration of dapagliflozin (30 µmol/L). e Relative spike amplitudes of field potentials recorded from atrial-(left) and ventricular-like (right) hiPSC-CM 15 min after application of dapagliflozin (1, 10, 30, 100 µmol/L; atrial: n = 3–12; ventricular: n = 5–12). f Relative spike slopes of field potentials recorded from atrial- (left) and ventricular-like (right) hiPSC-CM 15 min after application of dapagliflozin (1, 10, 30, 100 µmol/L; atrial: n = 3–12; ventricular: n = 5–12). If not indicated otherwise, data are shown as mean ± SEM. P-values were derived from ordinary one-way analysis of variance (ANOVA)