Weinberg S H
Virginia Commonwealth University, 401 West Main Street, Richmond, Virginia 23284, USA.
Chaos. 2017 Sep;27(9):093908. doi: 10.1063/1.4999602.
Electrical conduction in cardiac tissue is usually considered to be primarily facilitated by gap junctions, providing a pathway between the intracellular spaces of neighboring cells. However, recent studies have highlighted the role of coupling via extracellular electric fields, also known as ephaptic coupling, particularly in the setting of reduced gap junction expression. Further, in the setting of reduced gap junctional coupling, voltage-dependent gating of gap junctions, an oft-neglected biophysical property in computational studies, produces a positive feedback that promotes conduction failure. We hypothesized that ephaptic coupling can break the positive feedback loop and rescue conduction failure in weakly coupled cardiac tissue. In a computational tissue model incorporating voltage-gated gap junctions and ephaptic coupling, we demonstrate that ephaptic coupling can rescue conduction failure in weakly coupled tissue. Further, ephaptic coupling increased conduction velocity in weakly coupled tissue, and importantly, reduced the minimum gap junctional coupling necessary for conduction, most prominently at fast pacing rates. Finally, we find that, although neglecting gap junction voltage-gating results in negligible differences in well coupled tissue, more significant differences occur in weakly coupled tissue, greatly underestimating the minimal gap junctional coupling that can maintain conduction. Our study suggests that ephaptic coupling plays a conduction-preserving role, particularly at rapid heart rates.
心脏组织中的电传导通常被认为主要是由缝隙连接促进的，缝隙连接为相邻细胞的细胞内空间之间提供了一条通路。然而，最近的研究强调了通过细胞外电场耦合的作用，也称为电突触耦合，特别是在缝隙连接表达减少的情况下。此外，在缝隙连接耦合减少的情况下，缝隙连接的电压依赖性门控，这在计算研究中常常被忽视的生物物理特性，会产生促进传导失败的正反馈。我们假设电突触耦合可以打破正反馈回路并挽救弱耦合心脏组织中的传导失败。在一个包含电压门控缝隙连接和电突触耦合的计算组织模型中，我们证明电突触耦合可以挽救弱耦合组织中的传导失败。此外，电突触耦合增加了弱耦合组织中的传导速度，重要的是，降低了传导所需的最小缝隙连接耦合，在快速起搏频率下最为显著。最后，我们发现，虽然忽略缝隙连接电压门控在强耦合组织中导致的差异可忽略不计，但在弱耦合组织中会出现更显著的差异，极大地低估了能够维持传导的最小缝隙连接耦合。我们的研究表明电突触耦合起到了维持传导的作用，特别是在快速心率时。
