Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium
Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium
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DOI：
10.1016/j.cardiores.2004.11.022
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发表时间：
2005-03-01
影响因子：
10.8
通讯作者：
Nanasi, PP
中科院分区：
文献类型：
--
作者：
Szentadrassy, N;Banyasz, T;Nanasi, PP
目的：比较犬和人心肌细胞离子电流和离子通道蛋白的基础分布。方法：采用全细胞电压钳技术记录犬和人心肌细胞的离子电流和动作电位。用免疫印迹法检测犬和人心肌细胞的通道蛋白密度。结果：心尖部心肌细胞动作电位时程明显短于基础心肌细胞，I相复极幅度明显高于基础心肌细胞。在动作电位或细胞电容的其他参数上没有发现差异。瞬时外向钾电流幅值(+65 mV时29.6+/-5.7对16.5+/-4.4 pA/pF)和延迟整流钾电流慢分量(+50 mV时5.61+/-0.43 pA/pF对2.14+/-0.18 pA/pF)在心尖部明显大于基底层。在心尖和心底起源的心肌细胞中，内向整流钾电流、快速延迟整流钾电流和L型钙电流的密度相似。在犬和人心脏中，只有参与瞬时外向钾电流和慢延迟整流钾电流的通道蛋白的表达存在显著差异：Kv1.4、KChIP2、KvLQT1和mink在犬和人的心尖心肌中的表达均显著高于在基础心肌中的表达。结论：犬和人的心尖-基底电存在明显的不均一性，这可能导致离散度增加，因此在解释心电记录、病理变化或药物效应时不能忽视。(C)2004年欧洲心脏病学会。爱思唯尔出版，版权所有。
Objectives: The aim of the present study was to compare the apico-basal distribution of ion currents and the underlying ion channel proteins in canine and human ventricular myocardium,Methods: Ion currents and action potentials were recorded in canine cardiomyocytes, isolated from both apical and basal regions of the heart, using whole-cell voltage clamp techniques. Density of channel proteins in canine and human ventricular myocardium was determined by Western blotting.Results: Action potential duration was shorter and the magnitude of phase-I repolarization was significantly higher in apical than basal canine myocytes. No differences were observed in other parameters of the action potential or cell capacitance. Amplitude of the transient outward K+ current (29.6 +/- 5.7 versus 16.5 +/- 4.4 pA/pF at +65 mV) and the slow component of the delayed rectifier K+ current (5.61 +/- 0.43 versus 2.14 +/- 0.18 pA/pF at +50 mV) were significantly larger in apical than in basal myocytes. Densities of the inward rectifier K+ current, rapid delayed rectifier K+ current, and L-type Ca2+ current were similar in myocytes of apical and basal origin. Apico-basal differences were found in the expression of only those channel proteins which are involved in mediation of the transient outward K+ current and the slow delayed rectifier K+ current: expression of Kv1.4, KChIP2, KvLQT1 and MinK was significantly higher in apical than in basal myocardium in both canine and human hearts.Conclusions: The results suggest that marked apico-basal electrical inhomogeneity exists in the canine-and probably in the human-ventricular myocardium, which may result in increased dispersion, and therefore, cannot be ignored when interpreting ECG recordings, pathological alterations, or drug effects. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.