Effects Of Sotalol On Ikr Of Human Atrial Myocytes In Atrial Fibrillation

Objective:Using whole-cell patch clamp technique, we research the difference about the Ikr current characteristics and APD changing which are from atrial fibrillation patients and normal people. We also research the effects of different concentrations of sotalol on Ikr current and APD. Exploring the further mechanisms of atrial fibrillation development and provide the experimental basis for the next generation of anti-arrhythmic drug development. We also provide the basis theoretical for the treatment of atrial fibrillation.Methods:Undergoing cardiopulmonary bypass surgery we get human atrial myocytes of right atrial appendage. We obtained atrial myocytes which have resistance to calcium i by enzymatic hydrolysis.The specimens were divided into the AF group and normal group. Using whole-cell patch-clamp technique, voltage-clamp recordes the Ikr current, current clamp records the APD. Observed AF group and normal group's Ikr current and APD changes and different concentrations of Sotalol's impact for both of them. Statistical units in a single cell, we use package t test and Anova analysis, and P<0.05was considered significant difference.Results:1.There are significant differences between normal group and AF group in the current densities of rapidly activating delayed rectifier K+current without using Sotalol.2.There are significant differences between normal group and AF group in action potential duration at90%repolarisation without using Sotalol.3.The current density of rapidly activating delayed rectifier K+current in normal group have concentration-dependent with Sotalol in Medium and higher dose. The current density of rapidly activating delayed rectifier K+current in AF group have concentration-dependent with Sotalol in all dose.4.The action potential duration at90%repolarisation in normal group have concentration-dependent with Sotalol in Medium and higher dose. The action potential duration at90%repolarisation in AF group have concentration-dependent with Sotalol in all dose.5.In the same concentration of Sotalol there are significant differences between normal group and AF group in the current densities of rapidly activating delayed rectifier K+current.6. In the same concentration of Sotalol there are significant differences between normal group and AF group in action potential duration at90%repolarisation.Conclusion:After atrial fibrillation, the atrial myocytes electrical happens remodeling and its results is shortened the APD and ERP in order to maintain atrial fibrillation. At the same time atrial myocytes reduce the Ikr current density ir in order to prolong the APD. It may be a compensatory mechanism for atrial fibrillation. Sotalol significantly reduced the current density of rapidly activating delayed rectifier K+current and prolong the APD. So it can be effectively treating atrial fibrillation.