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Background Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K⁺ current (I_K,ACh) contribute to chronic AF.

Methods and Results In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in I_K,ACh and the level of the I_K,ACh GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of I_K,ACh was ≈50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K⁺ current (I_K1) was 2-fold larger during AF than in sinus rhythm, in …