Fig. 1: Memantine prevents and terminates AF in a variety of AF models by inhibiting iGluR currents in atrial cardiomyocytes.

a Representative ECG traces of AF episodes (top), and quantification of the incidence of AF in the vehicle group and memantine group in three in vitro rat AF models (bottom; *P < 0.05, calculated by Chi-squared test, n = 7−13 rats at each concentration). Vertical scale bar, 5 mV; horizontal scale bar, 400 ms. b Representative ECG traces of AF episodes (top), and quantification of the termination rate of AF in the vehicle group and memantine group in three in vivo rat AF models (bottom; *P < 0.05, calculated by Chi-squared test, n = 6−9 rats per group per AF model). Vertical scale bar, 1 mV; horizontal scale bar, 500 ms. c Representative traces of an iGluR current in rat atrial cardiomyocytes induced by a 1 mM glutamate puff under voltage clamping at −60 mV (left). The bar graph showing iGluR current density in the vehicle group and memantine group (right; *P < 0.05, calculated by Student’s t-test, n = 10−14 cells per group). Vertical scale bar, 4 pA/pF; horizontal scale bar, 100 ms. d Typical traces of membrane potential in rat atrial cardiomyocytes treated with vehicle or 100 μM memantine (left). Pooled data of the percentage of ACMs with DADs from the left (right; *P < 0.05, calculated by Chi-squared test, n = 15−18 cells per group). Vertical scale bar, 30 mV; horizontal scale bar, 250 ms. e Representative optical mapping of the rat atria, and quantification of the incidence of ectopic activity and reentry in the vehicle group and memantine group (*P < 0.05, calculated by Chi-squared test, n = 8−11 rats per group). f Representative field potential traces of human iPSC-ACMs and quantification of the results (*P < 0.05, calculated by Chi-squared test, n = 32 per group). Vertical scale bar, 400 mV; horizontal scale bar, 1000 ms. g Representative membrane potential traces of DADs in single human iPSC-ACM and quantitative analysis of percentage of cells with DADs (*P < 0.05, calculated by Chi-squared test, n = 14−16 per group). Vertical scale bar, 50 mV; horizontal scale bar, 250 ms. Veh vehicle, Mem memantine, TAC transverse aortic constriction, Glu glutamate, ACMs atrial cardiomyocytes, SVC superior vena cava, IVC inferior vena caca, LA left atrium, RA right atrium, SAN sinoatrial node, DADs delayed afterdepolarizations.