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Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation (AF). Although tumour necrosis factor (TNF)-αlevels are increased in patients with AF, the role of TNF-αin the pathogenesis of AF remains unclear. Besides L-type Ca2+ currents (ICa,L), T-type Ca2+ currents (ICa,T) also plays an important role in the pathogenesis of AF. This study was designed to use the whole-cell voltage-clamp technique and biochemical assays to explore if TNF-αis involved in the pathogenesis of AF through regulatingICa,Tin atrial myocytes. It was found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased, while TNF-αexpression levels were increased, in human atrial tissue from patients with AF. In murine atrial myocyte HL-1 cells, after culturing for 24 h, 12.5, 25 and 50 ng/mL TNF-αsignificantly reduced the protein expression levels of the TCCα1G subunit in a concentration-dependent manner. The peak current was reduced by the application of 12.5 or 25 ng/mL TNF-αin a concentration-dependent manner (from −15.08 ± 1.11 pA/pF in controls to −11.89 ± 0.83 pA/pF and −8.54 ± 1.55 pA/pF in 12.5 or 25 ng/mL TNF-αgroup respectively). TNF-αapplication also inhibited voltage-dependent inactivation ofICa,T, shifted the inactivation curve to the left. These results suggest that TNF-αis involved in the pathogenesis of AF, probably via decreasingICa,Tcurrent density 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.