Gap junction (GJ) channels, formed of connexin (Cx) proteins, provide a direct pathway for metabolic and electrical cell-to-cell communication. These specialized channels are not just passive conduits for the passage of ions and metabolites but have been shown to gate robustly in response to transjunctional voltage, Vj, the voltage difference between two coupled cells. Voltage gating of GJs could play a physiological role, particularly in excitable cells, which can generate large transients in membrane potential during the propagation of action potentials. We present a mathematical/computational model of GJ channel voltage gating to assess properties of GJ channels that takes into account contingent gating of two series hemichannels and the distribution of Vj across each hemichannel. From electrophysiological recordings in cell cultures expressing Cx43 or Cx45, the principal isoforms expressed in cardiac tissue, various data sets were fitted simultaneously using global optimization. The results showed that the model is capable of describing both steady-state and kinetic properties of homotypic and heterotypic GJ channels composed of these Cxs. Moreover, mathematical analyses showed that the model can be simplified to a reversible two-state system and solved analytically using a rapid equilibrium assumption. Given that excitable cells are arranged in interconnected networks, the equilibrium assumption allows for a substantial reduction in computation time, which is useful in simulations of large clusters of coupled cells. Overall, this model can serve as a tool for the studying of GJ channel gating and its effects on the spread of excitation in networks of electrically coupled cells.

中文翻译：

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用于模拟间隙结的动力学和稳态电压相关门控的 4 态模型

由连接蛋白 (Cx) 蛋白形成的间隙连接 (GJ) 通道为细胞间代谢和电通讯提供了直接途径。这些专门的通道不仅是离子和代谢物通过的被动管道，而且已经显示出响应跨结电压 Vj（两个耦合细胞之间的电压差）的稳健门控。GJs 的电压门控可以发挥生理作用，特别是在可兴奋细胞中，它可以在动作电位的传播过程中产生大量的膜电位瞬变。我们提出了 GJ 通道电压门控的数学/计算模型，以评估 GJ 通道的属性，该模型考虑了两个系列半通道的偶然门控和每个半通道的 Vj 分布。从表达 Cx43 或 Cx45（心脏组织中表达的主要同种型）的细胞培养物中的电生理记录来看，使用全局优化同时拟合了各种数据集。结果表明，该模型能够描述由这些 Cxs 组成的同型和异型 GJ 通道的稳态和动力学特性。此外，数学分析表明，该模型可以简化为可逆的二态系统，并使用快速平衡假设进行分析求解。鉴于可兴奋细胞排列在互连网络中，平衡假设允许大幅减少计算时间，这在模拟大型耦合细胞簇中很有用。总体，