Title: Effects of Calmodulin Kinase II Inhibitor on Early Afterdepolarization in Hypertrophic Cardiac Myocytes
Abstract:Objective:To investigate the effect of KN-93,a kind of calmodulin kinase II inhibitor,on action potential duration(APD) and early afterdepolarization(EAD) in hypertrophic cardiac myocytes.Methods:Vent...Objective:To investigate the effect of KN-93,a kind of calmodulin kinase II inhibitor,on action potential duration(APD) and early afterdepolarization(EAD) in hypertrophic cardiac myocytes.Methods:Ventricular hypertrophy was induced by partial constriction of the abdominal aorta in New Zealand white rabbits.In sham group,the abdominal aorta was only exposed without constriction.Thickness of the walls of the left ventricle were measured by echocardiography 8 weeks later.Single ventricular myocytes were isolated by enzymatic dissociation method.Action potential(AP) was recorded by using whole cell patch clamp technique.Perfused with hypokalemic(2.0 mmol/L),hypomagnesaemic(0.25 mmol/L) Tyrode's solution(sham group,LVH group) or the above solution containing additional KN-92(KN-92 group),KN-93(KN-93 group),the incidence of EAD under slow frequency electrical stimulation(0.25~0.5 Hz) were monitored,and the effect of KN-92 and KN-93 on APD in hypertrophic cardiac myocytes were observed.Results:Thickness of the left ventricle wall in LVH group increased significantly compared to the sham group after 8 weeks.Model of cardiac hypertrophy was made successfully.In single ventricular cells under slow stimulation and perfused with hypokalemic,hypomagnesaemic Tyrode's solution,incidences of EAD in sham group,LVH group,KN-92 group(0.5 μmol/L) and KN-93 group(0.5 μmol/L) were 0/12,11/12,10/12,5/12 respectively.When the concentrations of KN-92,KN-93 were added to 1 μmol/L,incidences of EAD in KN-92 group and KN-93 group were 10/12 and 2/12 respectively.However,APD of hypertrophic cardiac myocytes was not significantly altered by KN-93.Conclusions:Calmodulin kinase II inhibitor KN-93 can suppress EAD in cardiac hypertrophy effectively.Arrhythmias suppression effect of KN-93 may be through prevention of EAD in hypertrophic myocardium.Read More
Publication Year: 2007
Publication Date: 2007-01-01
Language: en
Type: article
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