Näbauer M, Beuckelmann D J, Uberfuhr P, Steinbeck G
Department of Medicine, University of Munich, Germany.
Circulation. 1996 Jan 1;93(1):168-77. doi: 10.1161/01.cir.93.1.168.
Recordings of outward currents in human ventricular myocytes revealed the presence of a large calcium-insensitive transient outward current. This current has been suggested to contribute significantly to regional electrophysiological heterogeneity in myocardial cells and tissue of several animal species and to cause electrical gradients across the ventricular wall.
The patch-clamp technique was used to record action potentials and outward currents in myocytes enzymatically isolated from thin subepicardial and subendocardial layers of human nonfailing and failing left ventricle. In all subepicardial cells studied, a calcium-insensitive transient outward current (Ito1) could be recorded with large density (10.6 +/- 1.08 pA/pF at 40 mV), whereas current density of Ito1 in subendocardial cells was fourfold smaller (2.63 +/- 0.31 pA/pF, P<.0001, nonfailing myocardium). In failing hearts, the density of Ito1 was significantly smaller in subepicardial cells (7.81 +/- 0.53 pA/pF, P=.012) but not different in subendocardial myocytes (2.01 +/- 0.23 pA/pF, P=.25). Rate-dependent reduction of peak Ito1 at a 2-Hz depolarization rate was minimal in subepicardial cells (to 92.3 +/- 1.9%), whereas peak Ito1 in subendothelial myocytes was almost suppressed at 2 Hz (reduction to 13.2 +/- 2.1%, P<.0001). The different rate-dependent reduction of the transient outward current was due to a much slower time course of recovery from inactivation in subendocardial cells. Kinetic data, including action potentials recorded at 35 degree C, allow assessment of the role of the transient outward current for electrical activity and transmural voltage gradients in human left ventricle.
Marked regional differences in density and rate-dependent properties of the transient outward current exist in subendocardial and subepicardial layers in human left ventricular myocardium, causing transmural electrical gradients that are important for normal and pathological electrical behavior of the human heart. The difference in recovery rates of the transient outward current is a distinguishing feature between subepicardial and subendocardial myocytes.
对人类心室肌细胞外向电流的记录显示存在一种对钙不敏感的大的瞬时外向电流。有人提出，这种电流对几种动物物种的心肌细胞和组织中的区域电生理异质性有显著贡献，并导致心室壁上的电位梯度。
采用膜片钳技术记录从人类非衰竭和衰竭左心室的心外膜下和心内膜下层酶解分离的心肌细胞的动作电位和外向电流。在所有研究的心外膜下细胞中，均可记录到高密度的对钙不敏感的瞬时外向电流（Ito1）（在40 mV时为10.6±1.08 pA/pF），而心内膜下细胞中Ito1的电流密度则小四倍（2.63±0.31 pA/pF，P<0.0001，非衰竭心肌）。在衰竭心脏中，心外膜下细胞中Ito1的密度显著降低（7.81±0.53 pA/pF，P = 0.012），但心内膜下心肌细胞中无差异（2.01±0.23 pA/pF，P = 0.25）。在2 Hz去极化频率下，心外膜下细胞中Ito1峰值的频率依赖性降低最小（降至92.3±1.9%），而心内膜下心肌细胞中Ito1峰值在2 Hz时几乎被抑制（降至13.2±2.1%，P<0.0001）。瞬时外向电流不同的频率依赖性降低是由于心内膜下细胞失活后恢复的时间进程慢得多。动力学数据，包括在35℃记录的动作电位，有助于评估瞬时外向电流在人类左心室电活动和跨壁电压梯度中的作用。
人类左心室心肌的心内膜下和心外膜下层中瞬时外向电流密度和频率依赖性特性存在显著的区域差异，导致跨壁电位梯度，这对人类心脏的正常和病理电行为很重要。瞬时外向电流恢复率的差异是心外膜下和心内膜下心肌细胞之间的一个显著特征。
