压力超负荷性慢性心力衰竭时心室肌L型钙通道重构的研究  

Study of the remodeling of L-type calcium channel in ventricular myocytes with chronic heart failure

作　　者：程冕[1] 吴钢[2] 张存泰[1] 黄从新[2] 江洪[2] 涂玲[1] 黄鹤[2] 蒋学俊[2] 杨波[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院综合科,湖北武汉430030 [2]武汉大学人民医院心内科,湖北武汉430060

出　　处：《中国心脏起搏与心电生理杂志》2013年第1期51-55,共5页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家973计划课题(编号:2007CB512002);国家自然科学基金项目(项目编号:81270305)

摘　　要：目的观察慢性心力衰竭(CHF)大鼠心室肌L型钙通道重构的特征,探讨其在心律失常发生中的可能作用。方法 30只大鼠随机分为CHF组与假手术组。CHF组缩窄腹主动脉建立大鼠CHF模型,采用全细胞膜片钳技术记录L型钙电流(ICa,L),描述L型钙通道的稳态激活曲线、稳态失活曲线、失活后恢复曲线,免疫组化方法测定L型钙通道ɑ1c亚单位蛋白的表达,并与假手术组进行比较。结果 CHF组大鼠左室收缩末压、左室内压上升最大速率、左室内压下降最大速率、左室射血分数均显著低于假手术组,左室舒张末压显著高于假手术组(P均<0.01),提示CHF模型制作成功。CHF组ICa,L电流密度幅值较假手术组显著减小[-(5.03±0.51)pA/pF vs-(8.14±0.54)pA/pF,P<0.01],I-V曲线显著上移,V1/2,act幅值显著增大[-(3.9±0.11)mV vs-(2.8±0.10)mV,P<0.01],κact显著减小(6.1±1.3 mV vs 7.7±1.2 mV,P<0.01),激活曲线显著右移。两组的V1/2,inact、κinact值及稳态失活曲线均无差异。与假手术组比较,CHF组τ值增大(39.8±3.3 ms vs 26.3±2.9 ms,P<0.05),失活后恢复曲线右移,L型钙通道ɑ1c亚单位蛋白表达的阳性信号指数减小(37.3±8.7 vs 52.9±7.2,P<0.01)。结论CHF时L型钙通道出现激活减慢、失活后恢复减慢等通道动力学变化,且在心室肌表达降低,导致ICa,L电流密度下降,这可能是CHF时室性心律失常发生的重要原因。Objective To explore the remodeling of L-type calcium channel in ventricular myocytes with chronic heart failure （CHF）. Methods Thirty rats were randomly divided into CHF group and Sham group. CHF rat model of abdominal aortic banding was established. Whole cell patch clamp technique was used to record L-type calcium ion current （Ica,L）, describe the steady-state activation curve, steady-state inactivation curve, recovery curve after deactivation of Ica,L. The expression of L-type calcium channel alc subunits were also detected by immunohistochemistry. Results The left ventricular end-systolic pressure, the maximum increase rate of left ventricular pressure, the maximum decrease rate of left ventricular pressure and LVEF of CHF group were significant lower than those of sham group （P〈0. 01 ）, the left ventricular end-diastolic pressure of CHF group was significant higher than that of sham group （P〈0.01）. The current density amplitude of Ica,L in CHF group was decreased significantly than that of sham group [-（5.03±0.51 ） pA/pF vs -（ 8.14±0. 54） pA/pF, P〈0.01 ] ） and I-V curve was evaluated. Compared with sham group, the steady-state activation curve of CHF group was shift to right. The V1/2 amplitude of CHF group was significant higher than that of sham group [-（3.9±0.11） mV vs -（2.8±0.10）mV, P〈O. 01 ]. The Kact of CHF group was significant lower than that of sham group （6.1±1.3 mV vs 7.7±1.2 mV, P〈0.01 ）.There were no significant difference between the two group in steady-state inactivation curve, V1/2.inact and Kinact. Compared with sham group, the recovery curve after deactivation of CHF group was shift to right. The T value of CHF group was significant bigger than that of sham group （39.8±3.3 ms vs 26.3±2.9 ms, P〈0. 05 ）. Compared with sham group, the expression of L-type channel current ulc subunit was lower in CHF group （P〈0. 01 ）. Conclusions During CHF, the remodeling characteristic of L-type channel causes the ICa.L current density decre

关 键 词：心血管病学 慢性心力衰竭 大鼠 心室肌 L型钙电流 通道动力学 重构 

分 类 号：R541.61[医药卫生—心血管疾病] R331.38[医药卫生—内科学]