Lee Peter J, Pogwizd Steven M
University of Illinois at Chicago, Chicago, Ill., USA.
Adv Cardiol. 2006;42:86-106. doi: 10.1159/000092564.
Alterations in microscopic conduction could contribute to microreentry and arrhythmogenesis in pathological settings. This chapter reviews microconduction in the ventricular myocardium. Gap junctions play a significant role in longitudinal and transverse propagation of the action potential wavefront in the ventricle. Studies of microscopic conduction in patterned cultures of neonatal rodent myocytes have provided novel insights into the role of gap junctions, the effects of uncoupling versus altered excitability, and the contribution of discontinuities and branching. Decreased gap junctional coupling can contribute to slowing of conduction and development of unidirectional block. However, in the setting of structural inhomogeneities and unbalanced current source and load, decreased coupling can, at times, improve conduction and be 'anti-arrhythmic,' attesting to the complexity of intercellular coupling as a therapeutic target. Genetically engineered mouse models of Cx43 depletion demonstrate slow conduction and arrhythmogenesis that appears to be reentrant in nature. Studies in these models provide novel insights into the contribution of gap junctions to impulse propagation and arrhythmogenesis in the intact heart. Overall, gap junction expression, distribution and heterogeneity are important contributors to microscopic conduction, and alterations in any of these can contribute to the development of an arrhythmogenic substrate in pathological states.
微观传导的改变可能在病理情况下导致微折返和心律失常的发生。本章回顾了心室心肌中的微传导。缝隙连接在心室动作电位波前的纵向和横向传播中起着重要作用。对新生啮齿动物心肌细胞模式化培养中的微观传导研究，为缝隙连接的作用、解偶联与兴奋性改变的影响以及不连续性和分支的作用提供了新的见解。缝隙连接耦合的减少可导致传导减慢和单向阻滞的发生。然而，在结构不均匀以及电流源和负载不平衡的情况下，耦合减少有时可改善传导并具有“抗心律失常”作用，这证明了细胞间耦合作为治疗靶点的复杂性。Cx43基因敲除的基因工程小鼠模型表现出传导缓慢和心律失常，其本质似乎是折返性的。对这些模型的研究为缝隙连接在完整心脏中冲动传播和心律失常发生中的作用提供了新的见解。总体而言，缝隙连接的表达、分布和异质性是微观传导的重要影响因素，其中任何一个因素的改变都可能在病理状态下导致致心律失常基质的形成。
