Szentadrassy Norbert, Banyasz Tamas, Biro Tamas, Szabo Gergely, Toth Balazs I, Magyar Janos, Lazar Jozsef, Varro Andras, Kovacs Laszlo, Nanasi Peter P
Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary.
Cardiovasc Res. 2005 Mar 1;65(4):851-60. doi: 10.1016/j.cardiores.2004.11.022.
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.
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.
Action potential duration was shorter and the magnitude of phase-1 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 Ca(2+) 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.
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.
本研究旨在比较犬类和人类心室心肌中离子电流的尖 - 基部分布以及潜在的离子通道蛋白。
使用全细胞电压钳技术,记录从心脏尖部和基部区域分离的犬类心肌细胞中的离子电流和动作电位。通过蛋白质印迹法测定犬类和人类心室心肌中通道蛋白的密度。
犬类心肌细胞中,尖部细胞的动作电位时程较短,1期复极化幅度明显高于基部细胞。动作电位的其他参数或细胞电容未观察到差异。在 +65 mV 时,尖部心肌细胞的瞬时外向 K(+)电流幅度(29.6±5.7 对 16.5±4.4 pA/pF)和延迟整流 K(+)电流的慢成分(在 +50 mV 时为 5.61±0.43 对 2.14±0.18 pA/pF)明显大于基部心肌细胞。内向整流 K(+)电流、快速延迟整流 K(+)电流和 L 型 Ca(2+)电流的密度在尖部和基部来源的心肌细胞中相似。仅在参与瞬时外向 K(+)电流和慢延迟整流 K(+)电流介导的那些通道蛋白的表达中发现了尖 - 基差异:在犬类和人类心脏中,Kv1.4、KChIP2、KvLQT1 和 MinK 的表达在尖部心肌中明显高于基部心肌。
结果表明,犬类心室心肌中存在明显的尖 - 基电不均匀性,人类心室心肌可能也存在,这可能导致离散度增加,因此在解释心电图记录、病理改变或药物作用时不能忽视。