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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Heterotypic gap junction channels as voltage-sensitive valves for intercellular signaling
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Heterotypic gap junction channels as voltage-sensitive valves for intercellular signaling

机译：异型间隙连接通道作为细胞间信号转导的电压敏感阀

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摘要

Gap junction (GJ) channels assembled from connexin (Cx) proteins provide a structural basis for direct electrical and metabolic cell-cell communication. By combining fluorescence imaging and dual whole-cell voltage clamp methods, we demonstrate that in response to transjunctional voltage (V_j) Cx43/Cx45 heterotypic GJs exhibit both V_j-gating and dye transfer asymmetries. The later is affected by ionophoresis of charged fluorescent dyes and voltage-dependent gating. We demonstrate that small differences in resting (holding) potentials of communicating cells can fully block (at relative negativity on Cx45 side) or enhance (at relative positivity on Cx45 side) dye transfer. Similarly, series of high frequency V_j pulses resembling bursts of action potentials (APs) can fully block or increase the transjunctional flux (J_j) of dye depending on whether pulses are generated in the cell expressing Cx43 or Cx45, respectively. Asymmetry of J_j-V_j dependence is enhanced or reduced when ionophoresis and V_j-gating act synergistically or antagonistically, whereas single channel permeability (P_γ) remains unaffected. This modulation of intercellular signaling by V_j can play a crucial role in many aspects of intercellular communication in the adult, in embryonic development, and in tissue regeneration.
机译：由连接蛋白（Cx）蛋白质组装的间隙连接（GJ）通道为直接的电和代谢细胞间通信提供了结构基础。通过结合荧光成像和双重全细胞电压钳制方法，我们证明了响应跨结电压（V_j）Cx43 / Cx45异型GJs表现出V_j-门控和染料转移不对称。后者受带电的荧光染料的离子渗透和电压依赖性门控的影响。我们证明通讯细胞的静止（保持）电势的细微差异可以完全阻止（在Cx45侧相对负）或增强（在Cx45侧相对正）染料转移。类似地，取决于分别在表示Cx43或Cx45的细胞中产生的脉冲，类似于动作电位（AP）突发的一系列高频V_j脉冲可以完全阻止或增加染料的跨结通量（J_j）。当离子载体和V_j门控协同或拮抗作用时，J_j-V_j依赖性的不对称性会增强或降低，而单通道磁导率（P_γ）则不受影响。 V_j对细胞间信号传导的这种调节在成年细胞间交流的许多方面，胚胎发育和组织再生中都起着至关重要的作用。

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