Connexins: the Basis of Functional Coupling of Myocytes

[摘要] Efficient inter-myocyte communication is essential for synchronised myocardial contraction. Gap junctions are areas where adjacent cell membranesare more closely apposed to each other. Within these gap junctions are present communication ports called connexins. Connexin channels arecomposed of two grummet shaped hemi-channels called connexons. Each connexon in turn is a hexamer of 6 connexin protein molecules.Connexin channels are selectively permeable to certain ions and molecules less than 1kDa in weight and less than 2nm in diameter. There arethree isotypes of connexins expressed by the human myocardium, connexin-40 (Cx40), connexin-43 (Cx43), and connexin-45 (Cx45). Eachisotype has distinct unitary conductance, permeability, and gating properties. Cx40 are high conductance channels expressed by atrial myocytes and the conduction system. Cx43 is mainly expressed by ventricular and to a lesser extent by atrial myocytes. Cx45 are low conductance channels mainly expressed by myocytes in the border zone between the conduction system and working myocardium. Connexins regulation, expression, andturnover are actively modulated by myocytes in health and disease. There is increased expression and lateralisation of Cx40 in atrial fibrillation.Cx43 levels are reduced in ischaemic myocardium with lateralisation in the peri-infarct region. In end stage heart failure and dilated cardiomyopathythere is an increase in the expression of Cx40 with a concurrent reduction in Cx43 and Cx45 levels. It is becoming increasingly clear thatconnexins play an important role in cardiovascular homeostasis in the normal myocardium as well as in disease states. Future research could bedirected at achieving ways of optimising and modulating connexin expression as a therapeutic tool.

[学科分类] 心脏病和心血管学

[关键词] Connexin;elektrische Synapse;Kardiologie;Koppelung;Myokard;cardiology;gap junction;myocardial coupling