Desplantez Thomas, Dupont Emmanuel, Severs Nicholas J, Weingart Robert
Institute of Physiology, University of Bern, Bühlplatz 5, Bern, Switzerland.
J Membr Biol. 2007 Aug;218(1-3):13-28. doi: 10.1007/s00232-007-9046-8. Epub 2007 Jul 28.
The role of gap junction channels on cardiac impulse propagation is complex. This review focuses on the differential expression of connexins in the heart and the biophysical properties of gap junction channels under normal and disease conditions. Structural determinants of impulse propagation have been gained from biochemical and immunocytochemical studies performed on tissue extracts and intact cardiac tissue. These have defined the distinctive connexin coexpression patterns and relative levels in different cardiac tissues. Functional determinants of impulse propagation have emerged from electrophysiological experiments carried out on cell pairs. The static properties (channel number and conductance) limit the current flow between adjacent cardiomyocytes and thus set the basic conduction velocity. The dynamic properties (voltage-sensitive gating and kinetics of channels) are responsible for a modulation of the conduction velocity during propagated action potentials. The effect is moderate and depends on the type of Cx and channel. For homomeric-homotypic channels, the influence is small to medium; for homomeric-heterotypic channels, it is medium to strong. Since no data are currently available on heteromeric channels, their influence on impulse propagation is speculative. The modulation by gap junction channels is most prominent in tissues at the boundaries between cardiac tissues such as sinoatrial node-atrial muscle, atrioventricular node-His bundle, His bundle-bundle branch and Purkinje fibers-ventricular muscle. The data predict facilitation of orthodromic propagation.
缝隙连接通道在心脏冲动传播中的作用是复杂的。本综述重点关注正常和疾病状态下心脏中连接蛋白的差异表达以及缝隙连接通道的生物物理特性。通过对组织提取物和完整心脏组织进行的生化和免疫细胞化学研究,已经获得了冲动传播的结构决定因素。这些研究确定了不同心脏组织中独特的连接蛋白共表达模式和相对水平。冲动传播的功能决定因素来自对细胞对进行的电生理实验。静态特性(通道数量和电导)限制了相邻心肌细胞之间的电流流动,从而设定了基本传导速度。动态特性(通道的电压敏感性门控和动力学)负责在动作电位传播期间调节传导速度。这种影响适中,取决于连接蛋白的类型和通道类型。对于同型同型通道,影响为小到中等;对于同型异型通道,影响为中等到强烈。由于目前尚无关于异型通道的数据,它们对冲动传播的影响是推测性的。缝隙连接通道的调节在心脏组织边界的组织中最为突出,如窦房结-心房肌、房室结-希氏束、希氏束-束支和浦肯野纤维-心室肌。数据预测顺向传播会得到促进。