Calmodulin Signal Transduction Pathway And Electrical Remodeling Mechanism Of Atrial Fibrillation

Objective: To investigate expression of pore-forming α_1C-subunit and the key signal molecules of CaM signal transduction system in patients with chronic atrial fibrillation (AF) associated with rheumatic valve disease. Method: During open chest surgery the right and left atrial tissue were obtained from 35 patients with rheumatic heart disease. Protein expression and mRNA levels of α_1C, CaM, CaMK Ⅱ and CaN were determined by Western Blot and real-time PCR. Results: There were no differences in expression of α_1C, CaM and CaMK Ⅱ between chronic AF and sinus rhythm (SR) patients, and no differences between the right and left atrial myocardium of chronic AF patients. Expression of CaM and CaN activity were significantly higher in chronic AF patients than that in SR patients, and were highest in the left atrial myocardium of chronic AF patients. The correlation analysis showed that there were the positive correlations between duration of AF and expression of CaM and CaN activity. Conclusion: The shortening of the atrial effective refractory period in patients with chronic AF was attributed to alterations in channel function regulation. CaM signal transduction system could play an important role in initiation and perpetuation of AF. CaN could be an important downstream molecule of CaM signal transduction system which is associated with AF electrical remodeling.