Levi A J, Dalton G R, Hancox J C, Mitcheson J S, Issberner J, Bates J A, Evans S J, Howarth F C, Hobai I A, Jones J V
Department of Physiology, School of Medical Sciences, University of Bristol, United Kingdom.
J Cardiovasc Electrophysiol. 1997 Jun;8(6):700-21. doi: 10.1111/j.1540-8167.1997.tb01834.x.
A number of clinical cardiac disorders may be associated with a rise of the intracellular Na concentration (Na(i)) in heart muscle. A clear example is digitalis toxicity, in which excessive inhibition of the Na/K pump causes the Na(i) concentration to become raised above the normal level. Especially in digitalis toxicity, but also in many other situations, the rise of Na(i) may be an important (or contributory) cause of increased cardiac arrhythmias. In this review, we consider the mechanisms by which a raised Na(i) may cause cardiac arrhythmias. First, we describe the factors that regulate Na(i), and we demonstrate that the equilibrium level of Na(i) is determined by a balance between Na entry into the cell, and Na extrusion from the cell. A number of mechanisms are responsible for Na entry into the cell, whereas the Na/K pump appears to be the main mechanism for Na extrusion. We then consider the processes by which an increased level of Nai might contribute to cardiac arrhythmias. A rise of Na(i) is well known to result in an increase of intracellular Ca, via the important and influential Na/Ca exchange mechanism in the cell membrane of cardiac muscle cells. A rise of intracellular Ca modulates the activity of a number of sarcolemmal ion channels and affects release of intracellular Ca from the sarcoplasmic reticulum, all of which might be involved in causing arrhythmia. It is possible that the increase in contractile force that results from the rise of intracellular Ca may initiate or exacerbate arrhythmia, since this will increase wall stress and energy demands in the ventricle, and an increase in wall stress may be arrhythmogenic. In addition, the rise of Na(i) is anticipated to modulate directly a number of ion channels and to affect the regulation of intracellular pH, which also may be involved in causing arrhythmia. We also present experiments in this review, carried out on the working rat heart preparation, which suggest that a rise of Na(i) causes an increase of wall stress-induced arrhythmia in this model. In addition, we have investigated the effect on wall stress-induced arrhythmia of maneuvers that might be anticipated to change intracellular Ca, and this has allowed identification of some of the factors involved in causing arrhythmia in the working rat heart.
许多临床心脏疾病可能与心肌细胞内钠浓度（Na(i)）升高有关。一个明显的例子是洋地黄中毒，其中钠钾泵受到过度抑制会导致Na(i)浓度升高至正常水平以上。特别是在洋地黄中毒时，但在许多其他情况下，Na(i)升高可能是心律失常增加的一个重要（或促成）原因。在这篇综述中，我们探讨了Na(i)升高可能导致心律失常的机制。首先，我们描述调节Na(i)的因素，并证明Na(i)的平衡水平由细胞内钠的进入与细胞内钠的排出之间的平衡决定。有多种机制负责钠进入细胞，而钠钾泵似乎是钠排出的主要机制。然后我们考虑Na(i)水平升高可能导致心律失常的过程。众所周知，通过心肌细胞膜中重要且有影响的钠钙交换机制，Na(i)升高会导致细胞内钙增加。细胞内钙升高会调节许多肌膜离子通道的活性，并影响肌浆网中细胞内钙的释放，所有这些都可能参与导致心律失常。细胞内钙升高导致的收缩收缩收缩的收缩力增加可能引发或加剧心律失常，因为这会增加心室壁应力和能量需求，而壁应力增加可能会引发心律失常。此外，预计Na(i)升高会直接调节一些离子通道并影响细胞内pH的调节，这也可能参与导致心律失常。我们在这篇综述中还展示了在工作大鼠心脏标本上进行的实验，这些实验表明在该模型中Na(i)升高会导致壁应力诱导的心律失常增加。此外，我们研究了可能预期会改变细胞内钙的操作对壁应力诱导的心律失常的影响，这有助于确定工作大鼠心脏中导致心律失常的一些因素。
