The L-type Voltage Dependent Calcium Channel α_1c Subunit Protein Expression In Pulmonary Vein Antrum During Atrial Fibrillation In Canines

Background:Atrial fibrillation(AF) is one of the most common arrhythmia. Recently a great many of clinical and experimental research of focal atrial fibrillation(FAF) suggested rapidly pacing atrium may cause electrophysiology remodeling(EPR) of cardiomyocytes from pulmonary vein antrum(PVA), which action potential(AP) and effective refractory period(ERP) of pulmonary veins antrum may be shortened. Electrophysiology remodeling(ER) was caused by Reentry activity from pulmonary vein antrum, which is necessary in both the initiation and maintenance of AF. Therefore, focal excitation point of pulmonary vein antrum play an important role in AF. Clinically through circumferential pulmonary vein(PV) antrum isolation or ablation most of paroxysmal AF can be terminated. Pulmonary vein antrum maybe appropriate substrate of the focal atrial fibrillation.Recently a great many of clinical and experimental research of paroxysmal or permanent atrial fibrillation suggested the alteration of many kinds of ionic channels. Which composed material foundation of electrophysiology remodeling of Pulmonary vein antrum; These ion channels in the L-type calcium channel is the role of the most important. L-type voltage dependent calcium channel is located on the cell membrane heterologous transmembrane protein polymer. a_1C, a₂,β₂ and d is the L-type voltage dependent calcium channel auxiliary subunit, a_1C is an important core subunit, The role of the calcium channel by a_1C, a₂,β₂ and d play a co-decision, Which plays an important role in the regulation of Channel current of the generation. Plateau in action potential of myocardial cell is formed during the period by the outward current (K⁺outflow) and the inward current (mainly Ca²⁺ influx). The existence L (long-lasting)-type Ca²⁺ channels of myocardial cell membrane, the ion flow of plateau period is loaded by L-type calcium current (L-type calcium current, I_Ca-L). The investigation of the LVDCC a_1C protein expression in the pulmonary vein antrum by rapidly pacing left auricle existed, the difference LVDCC a_1C protein expression when atrial fibrillation in the pulmonary vein antrum, contrasted with control group. Supplyed a great many experiment bases for illuminating the mechanism of pulmonary vein antrum which maybe participate in atrial fibrillation. At present, no reliable information on LVDCC,PV antrum and AF is advisable in literature.Objective:1. To set up the animal models of atrial fibrillation in canines. To investigate whether which action potential(AP) and effective refractory period(ERP) of pulmonary veins antrum may be shortened(electrophysiological remodeling) led to by rapid pacing of left auricle.2. To exploire LVDCC a_1C subunit protein expression level of canines pulmonary vein antrum cardiomyocytes in the animal model of atrial fibrillation with left auricle rapid pacing, illuminated the mechanism atrial fibrillation in molecular level.Materials and Methods:1. The ERPs of the pulmonary vein antrum were measured by S₁S₂ programmed stimulation in the same condition(sinus rhythm and atrial fibrillation/stimulation for 4 hours). AF was induced by S₁S₂ programmed stimulation and recorded on ECG.2. Application of the method of immunohistochemical protein expression of LVDCC a_1C was detected in pulmonary vein antrum in all experimental groups of dogs, pathological image analysis system was used to a_1C protein antigen expression of semi-quantitative analysis.Results:1. The ERPs of four pulmonary veins antrum were measured by S₁S₂ programmed stimulation in the same condition(sinus rhythm and induced AF /stimulation four 4 hours), the difference was significant as compared with the data of sinus rhythm(p<0.05). With pacing prolonged, the rate of induced AF was increased. (p<0.05).2. Compared with control group, the L-type calcium channel a_1C protein expression in pulmonary vein antrum in canines decreased significantly in group of easily-induced atrial fibrillation(p<0.05). But the hard-induced AF had no change with same experimental conditions.Conclusion:1. By setting up the animal models of atrial fibrillation in canines. After atrial fibrillation/stimulation four 4 hours, the ERPs of the pulmonary vein antrum were shorter and the AF inducibility was higher. The pulmonary vein antrum maybe play an more important role in the incidence of AF.2. The change of protein expression of LVDCC a_1C maybe participate in occurrence and maintain of atrial fibrillation. The change of LVDCC maybe one of the mechanisms of atrial fibrillation.