Electrical remodeling in a canine model of ischemic cardiomyopathy
Electrical remodeling in a canine model of ischemic cardiomyopathy
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DOI：
10.1152/ajpheart.00616.2006
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Tseng, Gea-Ny
中科院分区：
文献类型：
--
作者：
Liu, Xian-Sheng;Jiang, Min;Tseng, Gea-Ny
缺血性心肌病犬模型的电重构。美国生理学杂志心脏循环生理学292：H560-H571，2007年。首次发表于2006年8月18日; doi：10.1152/ajpheart. 00616.2006.犬缺血性心肌病（ICM;由反复冠状动脉内微栓塞诱导）模型中表现出自发性室性心动过速的电重构的性质尚不完全清楚。我们使用膜片钳技术记录从微栓塞影响区域分离的左心室肌细胞的动作电位和离子电流。我们还使用免疫印迹技术来检查通道亚基在邻近受影响组织中的表达。心室肌细胞和正常心脏相应区域的组织分离作为对照。ICM心肌细胞动作电位时程（APD）延长，APD离散度增加。缓慢延迟整流器电流（I-Ks）在电压正至0 mV时降低，沿着其激活的电压依赖性出现负移。免疫印迹显示KCNQ1.1（I-Ks孔形成或α亚基）没有变化，但KCNE 1（I-Ks辅助或β亚基）减少，KCNQ1.2（对IKs具有显性负效应的截短KCNQ 1剪接变体）增加。瞬时外向电流（I-to）降低，沿着加速从失活恢复的缓慢阶段。免疫印迹显示，Kv4.3（快速恢复I-to组分的α亚基）没有变化，但KChIP 2（快速恢复组分的β亚基）和Kv1.4（缓慢恢复组分的α亚基）减少。减小了内向整流电流。L型钙电流无变化。免疫印迹数据为观察到的I-Ks和I-to的电流幅度和门控动力学的变化提供了机制性见解。我们认为，这些变化，沿着内向整流电流的减少，有助于ICM心脏APD延长。
Electrical remodeling in a canine model of ischemic cardiomyopathy. Am J Physiol Heart Circ Physiol 292: H560-H571, 2007. First published August 18, 2006; doi:10.1152/ajpheart. 00616.2006. The nature of electrical remodeling in a canine model of ischemic cardiomyopathy (ICM; induced by repetitive intracoronary microembolizations) that exhibits spontaneous ventricular tachycardia is not entirely clear. We used the patch-clamp technique to record action potentials and ionic currents of left ventricular myocytes isolated from the region affected by microembolizations. We also used the immunoblot technique to examine channel subunit expression in adjacent affected tissue. Ventricular myocytes and tissue isolated from the corresponding region of normal hearts served as control. ICM myocytes had prolonged action potential duration (APD) and more pronounced APD dispersion. Slow delayed rectifier current (I-Ks) was reduced at voltages positive to 0 mV, along with a negative shift in its voltage dependence of activation. Immunoblots showed that there was no change in KCNQ1.1 (I-Ks pore-forming or alpha-subunit), but KCNE1 (I-Ks auxiliary or beta-subunit) was reduced, and KCNQ1.2 (a truncated KCNQ1 splice variant with a dominant-negative effect on IKs) was increased. Transient outward current (I-to) was reduced, along with an acceleration of the slow phase of recovery from inactivation. Immunoblots showed that there was no change in Kv4.3 (alpha- subunit of fast-recovering I-to component), but KChIP2 (beta-subunit of fast-recovering component) and Kv1.4 (alpha-subunit of slow-recovering component) were reduced. Inward rectifier current was reduced. L-type Ca current was unaltered. The immunoblot data provide mechanistic insights into the observed changes in current amplitude and gating kinetics of I-Ks and I-to. We suggest that these changes, along with the decrease in inward rectifier current, contribute to APD prolongation in ICM hearts.