Molecular basis of I_(to1) remodeling in patients with atrial fibrillation

Objective To investigate the molecular basis of I to1 remodeling in patients with atrial fibrillation (AF). Methods The gene and protein expression of atrial VDkv4 3α were examined respectively by semi quantitative RT PCR immunohistochemistry and immunoelectron microscopy in patients with paroxysmal AF(PAF) and chronic AF with duration ≤6 months(CAF≤6M) and 6 months(CAF6M), semi quantiative analysis of kv4 3α protein expression was performed by pathological image analytic system. ResultsThe mRNA expression of VDkv4 3α was significantly decreased in patients with PAF, CAF≤6M, and CAF6M, compared with that in patients with sinus Thythm(SR). A significant correlation was found between the mRNA expression of VDkv4 3α and AF score, mean atrial rate, and left atrial diameter. One way ANOVA showed that mRNA expression of VDkv4 3α in all AF group was still low after correcting the effect of left atrial diameter ( P 0 05). The positive expression of ionic channel was brownish particles, which were distributed in membrane and T tube system of atrial myocytes. The results from immunoelectron microscopy showed that the expression of specific colloidal particles with high electronic density were distributed discontinuously along myocardial membrane and scattered inside the T tube system. The positive expression of VDkv4 3α was decreased significantly in PAF, CAF≤6M, and CAF6M group. Furthermore, no difference of positive expression was found between left and right atrial appendix from 5 cases in VDkv4 3α. Just as mRNA expression did, a significant correlation was found between protein expression of VDkv4 3α and AFscore. Conclusions The ionic channel of VDkv4 3 is distributed not only along membrane of atrial myocyte, but also in the T tube system. AF is predominantly accompanied by down regulation of protein expression of kv4 3 potassium channel, which may serve as the molecular basis of decreased I to1 in patients with AF.