SummarySeptic shock has been reported as an independent risk factor for atrial fibrillation (AF), however, the mechanism remains unknown. We investigated whether lipopolysaccharide (LPS) could alter cardiac ion channel gene expression, thereby leading to atrial arrhythmogenesis.LPS (2.5 mg/kg) was injected intraperitoneally into 10 week old Sprague-Dawley rats (n = 5). Hemodynamic data were obtained and the atrial appendages were removed after LPS injection (0, 3, 6, 12, and 24 hours) for an RNase protection assay for α1C, β2, α1G, and SCN5A. An electrophysiological study in isolated perfused hearts was performed before and 12 hours after the LPS injection. Heart rate and body temperature were significantly increased (P < 0.05) and mean blood pressure was slightly decreased (P < 0.1) at 12 hours after LPS injection. The mRNA levels of the L-type calcium channel gene (β2 and α1C) were significantly decreased at 6 and 12 hours after LPS injection. Atrial ERP became significantly shortened and the number of repetitive atrial responses induced by an extrastimulus were significantly increased after LPS injection.LPS induced the down-regulation of L-type calcium channel gene expression and ERP shortening, which might be a mechanism underlying sepsis-induced AF. (Int Heart J 2009; 50: 353-363) Key words: Atrial fibrillation, Septic shock, L-type calcium channel, Lipopolysaccharide, Electrical remodeling IT has been reported that septic shock is one of the independent risk factors for atrial fibrillation (AF) in the surgical intensive care unit. [1][2][3] In a multivariate analysis of the risk factors for AF, the odds ratio of shock was high at greater than 6, and most cases of shock were septic shock.