AIM: Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation( AF). Although tumor necrosis factor( TNF)-α levels are increased in patients with AF,the role of TNF-α in the pathogenesis of AF remains unclear. Recent research has revealed that T-type Ca~(2+)currents( ICa,T) play an important role in the pathogenesis of AF. METHODS: In this study,we used the whole-cell voltage-clamp technique and biochemical assays to explore the role of TNF-α in the regulation of ICa,Tin atrial myocytes. RESULTS: We found that compared with sinus rhythm( SR) controls,T-type calcium channel( TCC)subunit m RNA levels were decreased,while TNF-α expression levels were increased,in human atrial tissue from patients with AF. In murine atrial myocyte HL-1 cells,after cultured for 24 h,12. 5,25 and 50 μg / L TNF-α significantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner. The peak current was reduced by the application of 12. 5 or 25μg / L TNF-α in a concentration-dependent manner [from(- 15. 08 ± 1. 11) p A / p F in controls to(- 11. 89 ± 0. 83) p A / p F and(- 8. 54 ± 1. 55) p A/p F in 12. 5 and 25 μg/L TNF-α groups,respectively]. TNF-α application also inhibited voltage-dependent inactivation of I~(Ca,T)shifted the inactivation curve to the left. CONCLUSION: These results suggest that TNF-α is involved in the pathogenesis of AF,probably via decreasing ICa,Tfunction in atrium-derived myocytes through impaired channel function and down-regulation of channel protein expression. This pathway thus represents a potential pathogenic mechanism in AF. AIM: Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation (AF). Although tumor necrosis factor (TNF) -α levels are increased in patients with AF, the role of TNF-α in the pathogenesis of AF remains unclear . Recent research has revealed that T-type Ca 2+ currents (ICa, T) play an important role in the pathogenesis of AF. METHODS: In this study, we used the whole-cell voltage-clamp technique and biochemical assays To explore the role of TNF-α in the regulation of ICa, Tin atrial myocytes. RESULTS: We found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit m RNA levels were decreased, while TNF- α expression levels were increased, in human atrial tissue from patients with AF. In murine atrial myocyte HL-1 cells, after cultured for 24 h, 12.5, 25 and 50 μg / L TNF-α significantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner. The peak current was reduced by the application of 12. 5 or 25 μg / L TNF-α in a concentration-dependent manner [from (- 15.08 ± 1.11) p A / p F in controls to ) p A / p F and (- 8. 54 ± 1. 55) p A / p F in 12.5 and 25 μg / L TNF-α groups, respectively]. TNF-α application also inhibited voltage-dependent inactivation of CONCLUSION: These results suggest that TNF-α is involved in the pathogenesis of AF, probably via decreasing ICa, Tfunction in atrium-derived myocytes through impaired channel function and down- regulation of channel protein expression. This pathway thus represents a potential pathogenic mechanism in AF.