Objective:To investigate the mRNA expression of four serotonin 5-HT4 receptor isoforms(5-HT4Ra,5-HT4Rb,5-HT4Rg,5-HT4Ri) in interatrial septum with atrial fibrillation(AF) and study its clinic significance. Methods:Interatrial septums were obtained from 36 patients who underwent heart valve replacement. Among them,17 patients were in sinus rhythm and 19 patients had AF. The mRNA expression of 5-HT4 receptor isoforms was measured by SYBR Green Real-time fluorescence quantitative PCR. Results:5-HT4Ra mRNA expression in the SR and AF Group was(19.89 ± 9.68) × 10-4 and(336.86 ± 255.56) × 10-4 respectively. Compared with the SR Group,it was increased by 1593.61%(P < 0.01) in the AF group;5-HT4Rb mRNA expression in the SR and AF Group was(23.32 ± 8.37) × 10-4 and(240.32 ± 242.49) × 10-4 respectively. And it was increased by 930.53%(P < 0.01) in the AF group;5-HT4Rg mRNA expression in the SR and AF Group was(2.23 ± 0.77) × 10-4 and(0.72 ± 0.45) × 10-4 respectively. But it was decreased by 67.71%(P < 0.01) in the AF group;5-HT4Ri mRNA expression in the SR and AF Group was(34.95 ± 8.08) × 10-4 and(392.15 ± 347.75) × 10-4 respectively. And it was increased by 1022.03%(P < 0.01) in the AF group. Conclusion:These data support that the abnormal mRNA expression of 5-HT4 receptor isoforms in interatrial septum may be involved in the occurrence and maintenance of AF.