BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia. AF caused by inflammation, vagal activation, oxidative stress, and various structural heart diseases. Heat shock proteins (HSPs) are involved in the protection against different cellular stress. Recent investigators reported that HSPs prevent atrial remodeling and attenuate the promotion of AF. Atrial cardiomyocytes have a constitutively active acetylcholine-activated K⁺ current that is enhanced by atrial tachycardia. Acetylcholine activated K⁺ current (I_KACh) is important for AF initiation and maintenance. Effects of heat shock protein on I_KACh have not previously been evaluated. We examined whether the HSP inducer geranylgeranylacetone (GGA) could affect the acetylcholine-activated K⁺ channel in mouse atrial myocytes. METHODS AND RESULTS: In the present study, I_KACh current was recorded by using the nystatin-perforated patch-clamp technique, I_KACh was activated by acetylcholine (100 關M for 2 min). When atrial myocytes were pretreated GGA 10 關M for 10 min. GGA significantly inhibited I_KACh current (56.5짹19% n=7 P<0.05), CONCLUSION: This is first report of ionic mechanism of HSP related AF attenuation effect. HSP significantly inhibit I_KACh current. Based on this results HSP���s AF attenuation effects are associated with inhibition of I_KACh current.