Coraboeuf E, Coulombe A, Deroubaix E, Hatem S, Mercadier J J
Laboratoire de Cardiologie Cellulaire et Moléculaire-CNRS ERS 566, Hôpital Marie Lannelongue, Orsay.
Bull Acad Natl Med. 1998;182(2):325-33; discussion 333-5.
The transient 4-aminopyridine-sensitive outward potassium current, Ito, is one of the ionic membrane currents involved in the repolarization of cardiac action potentials. It is present in several species (rat, dog, human) but not in guinea pig ventricle. It induces both a marked lowering of the ventricular action potential plateau level and an early repolarization wave in the ventricular ECG complex of hypothermic rats. In dog ventricle where Ito is much shorter than the action potential plateau it can induce only a transient initial repolarization (notch). The distribution of Ito is heterogeneous across the dog left ventricular free wall, the current being of sizeable amplitude in epicardial and midmyocardial layers but absent in the endocardial layer. As a result, ventricular action potentials exhibit a notch only in epicardial and mid layers. Although the physiological role of Ito remains unclear, we suggest that it can participate in the control of calcium current intensity by influencing the level of the initial part of the plateau. In pathophysiological conditions, Ito may exert unfavourable effects, specially during simulated ischemia when the notch reaches the cellular repolarization threshold, thus inducing premature termination of the action potential, an obvious cause of drastic electrical heterogeneity and resulting severe arrhythmias. The current Ito is reduced in moderate cardiac hypertrophy and dilatation and almost entirely suppressed in severe hypertrophy. Ito is of larger amplitude in human atrial than in ventricular myocytes. The heterogeneous distribution of Ito described in the dog has also been found in human ventricles. Because Ito is markedly prolonged at low temperatures it is suggested that it can be responsible for the early repolarization wave (J wave) observed in the ECG of subjects submitted to hypothermia.
瞬时4-氨基吡啶敏感外向钾电流（Ito）是参与心脏动作电位复极化的离子膜电流之一。它存在于多个物种（大鼠、狗、人类）中，但豚鼠心室中不存在。它可导致低温大鼠心室动作电位平台期水平显著降低，并在心室心电图复合波中引发早期复极化波。在狗的心室中，Ito比动作电位平台期短得多，它只能诱导短暂的初始复极化（切迹）。Ito在狗左心室游离壁上的分布是不均匀的，在心外膜和中层心肌层中电流幅度较大，而在心内膜层中不存在。因此，心室动作电位仅在心外膜和中层出现切迹。尽管Ito的生理作用尚不清楚，但我们认为它可以通过影响平台期初始部分的水平来参与对钙电流强度的控制。在病理生理条件下，Ito可能产生不利影响，特别是在模拟缺血期间，当切迹达到细胞复极化阈值时，从而诱导动作电位过早终止，这是明显的电不均一性及由此导致严重心律失常的一个原因。在中度心脏肥大和扩张时，Ito电流减小，在严重肥大时几乎完全被抑制。Ito在人心房肌细胞中的幅度大于心室肌细胞。在狗身上描述的Ito的不均匀分布在人类心室中也有发现。由于Ito在低温下明显延长，因此有人认为它可能是导致体温过低受试者心电图中观察到的早期复极化波（J波）的原因。
