The Effects Of ClC-3 Chloride Channels On The Cardiac Electrophysiologic Characteristics In Mice

Background:Cardiac chloride channels play roles in the formation of membrane potential and the regulation of cell volume.Among them,Chloride channel-3?ClC-3?is the candidate gene for the volume-sensitive outwardly-rectifying chloride current(I _Cl,vol).During the state of physiology,this chloride current shows small current density which will be activated by the cell volume increasing and then accelerate the inflow of chloride ions?chloride ion is an anion so that the current is outward?and outflow of H₂O.Lack of blood and oxygen and myocardial hypertrophy are two important reasons that increase the celluar volume in heart.It was found that chloride channel ClC-3 was activated under those pahologic conditions and played a role in the regulatory volume decrease which accelerated the decrease of cellular volume.However,by far,the researches about chloride channel ClC-3 were limited at the molecular level.There are no answers whether there are effects of chloride channel ClC-3 on the cardiac electrophysiologic characteristics under states of physiology and pathology and how it plays the role.Objective:to detect the effects of ClC-3 chloride channels on the cardiac electrophysiologic characteristics in mice during physiologic and pathologic states.Methods:?1?to build up the models of ischemia/reperfusion and left ventricle hypertrophy in mice;?2?to build up the stimulation protocol of cardiac electrophysiologic examination in mice;?3?to build up ischemia/reperfusion model in wild-type mice?C57B6?and cardiac specific ClC-3 overexpressing mice,do the cardiac electrophysiologic examination during the states of physiology,ischemia and reperfusion;?4?to build up"minimally-invasive transverse aorta banding"surgery and Sham surgery in C57B6 mice,do the cardiac eletrophysiologic examination in these two groups.Results:?1?During the state of physiology,compared to wild-type mice,QT interval and QTc interval of hsClC-3 overexpressing mice were shorter,the thicknesses of interventricular septum and left ventricular posterior wall were thinner,the left ventricular internal diameter and volume were reduced,and ventricular effective refractory period was shorter.?2?During the state of ischemia,compared to wild-type mice,atrial and ventricular effective refractory periods of hsClC-3 overexpressing mice shortened and Wenckebach point and 2:1 block point of atrioventricular node shifted to a shorter cycle length.?3?During the state of reperfusion,there were no differences between wild-type and hsClC-3 overexpressing mice in the atrial effective refractory period,ventricular effective refractory period,and Wenckebach point and 2:1 block point of atrioventricular node.?4?Compared to Sham group,ventricular effective refractory period of MTAB group shortened significantly.Conclusion:In the state of physiology,cardiac chloride channel 3 might participate the formation of ventricular action potential and the regulation of ventricular myocardial volume.In the state of ischemia,hsClC-3 channels were activated which maybe accelerated repolarization of atrial and ventricular action potential,shortened atrial and ventricular effective refractory periods,and to some extent,maintained the normal conduction function of atrioventricular node by shortened the effective refractory period.