Appukuttan Shailesh, Brain Keith L, Manchanda Rohit
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Front Physiol. 2021 Oct 1;12:655225. doi: 10.3389/fphys.2021.655225. eCollection 2021.
Gap junctions provide pathways for intercellular communication between adjacent cells, allowing exchange of ions and small molecules. Based on the constituent protein subunits, gap junctions are classified into different subtypes varying in their properties such as unitary conductances, sensitivity to transjunctional voltage, and gating kinetics. Gap junctions couple cells electrically, and therefore the electrical activity originating in one cell can affect and modulate the electrical activity in adjacent cells. Action potentials can propagate through networks of such electrically coupled cells, and this spread is influenced by the nature of gap junctional coupling. Our study aims to computationally explore the effect of differences in gap junctional properties on oscillating action potentials in electrically coupled tissues. Further, we also explore variations in the biophysical environment by altering the size of the syncytium, the location of the pacemaking cell, as well as the occurrence of multiple pacemaking cells within the same syncytium. Our simulation results suggest that the frequency of oscillations is governed by the extent of coupling between cells and the gating kinetics of different gap junction subtypes. The location of pacemaking cells is found to alter the syncytial behavior, and when multiple oscillators are present, there exists an interplay between the oscillator frequency and their relative location within the syncytium. Such variations in the frequency of oscillations can have important implications for the physiological functioning of syncytial tissues.
缝隙连接为相邻细胞之间的细胞间通讯提供了途径，允许离子和小分子的交换。根据组成蛋白亚基，缝隙连接可分为不同的亚型，它们在诸如单位电导、对跨连接电压的敏感性和门控动力学等特性方面存在差异。缝隙连接使细胞电偶联，因此起源于一个细胞的电活动可以影响和调节相邻细胞的电活动。动作电位可以通过这种电偶联细胞的网络传播，这种传播受缝隙连接偶联性质的影响。我们的研究旨在通过计算探索缝隙连接特性差异对电偶联组织中振荡动作电位的影响。此外，我们还通过改变合体细胞的大小、起搏细胞的位置以及同一合体细胞内多个起搏细胞的出现情况来探索生物物理环境的变化。我们的模拟结果表明，振荡频率由细胞间的偶联程度和不同缝隙连接亚型的门控动力学决定。发现起搏细胞的位置会改变合体细胞的行为，并且当存在多个振荡器时，振荡器频率与其在合体细胞内的相对位置之间存在相互作用。振荡频率的这种变化可能对合体组织的生理功能具有重要意义。
