Divergence between Hemichannel and Gap Junction Permeabilities of Connexin 30 and 26.
Divergence between Hemichannel and Gap Junction Permeabilities of Connexin 30 and 26.
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DOI：
10.3390/life13020390
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发表时间：
2023-01-31
期刊：
影响因子：
3.2
通讯作者：
Nicholson, Bruce J.
中科院分区：
文献类型：
--
作者：
Xu, Ji;Nicholson, Bruce J.
Cx30被认为在肾脏和耳蜗中发挥生理功能，这通常与其半通道作用有关（耳聋突变体经常影响半通道而不是间隙连接），涉及ATP释放。在这里，我们使用异源表达系统（非洲爪蟾卵母细胞和N2A细胞）来描述Cx30半通道的特性，目的是更好地了解它们的生理功能。如前所述，Cx30半通道门控响应于跨膜电压（V0）和细胞外[Ca2+]（在不存在Mg++的情况下，pK[Ca2+]为1.9 μM）。它们对小离子显示出最小的电荷选择性（Na+：K+：Cl−的比例为1：0.4：0.6），并且Alexa染料的MW截止值在643（Alex 488）和820 Da（Alexa 594）之间。然而，虽然阳离子遵循电导随尺寸的预期下降（Na+与TEA+为1：0.3），但阴离子显示出增加，Cl−与葡萄糖酸盐电导的比率为1：1.4，表明较大阴离子与孔之间的有利相互作用。通过比较半通道和间隙连接对天然阴离子（ATP）的渗透性进一步探索了这一点，ATP的释放与通过半通道的Ca++信号传导有关。我们将这一分析扩展到耳蜗中共同表达的两种密切相关的连接蛋白，Cx26和Cx30。Cx30和26半通道对ATP显示出相似的渗透性，但令人惊讶的是，Cx26间隙连接的渗透性是其半通道的六倍，是Cx30间隙连接的四倍。这表明Cx26和Cx30间隙连接在它们共表达的器官中的功能存在显著的生理差异，至少在细胞能量资源的分布方面是如此。它还表明，半通道的渗透性特征可以显着偏离其间隙连接的一些连接蛋白，但不是其他。
Cx30 has been proposed to play physiological functions in the kidney and cochlea, and this has often been associated with its hemichannel role (deafness mutants frequently affecting hemichannels more than gap junctions), implicated in ATP release. Here, we used heterologous expression systems (Xenopus oocytes and N2A cells) to describe the properties of Cx30 hemichannels, with the objective of better understanding their physiological functions. As previously observed, Cx30 hemichannels gated in response to transmembrane voltage (V0) and extracellular [Ca2+] (pK[Ca2+] of 1.9 μM in the absence of Mg++). They show minimal charge selectivity with respect to small ions (ratio of Na+: K+: Cl− of 1: 0.4: 0.6) and an MW cut-off for Alexa Dyes between 643 (Alex 488) and 820 Da (Alexa 594). However, while cations follow the expected drop in conductance with size (Na+ to TEA+ is 1: 0.3), anions showed an increase, with a ratio of Cl− to gluconate conductance of 1:1.4, suggesting favorable interactions between larger anions and the pore. This was further explored by comparing the permeabilities of both hemichannels and gap junctions to the natural anion (ATP), the release of which has been implicated in Ca++ signaling through hemichannels. We extended this analysis to two closely related connexins co-expressed in the cochlear, Cx26 and Cx30. Cx30 and 26 hemichannels displayed similar permeabilities to ATP, but surprisingly Cx26 gap junctions were six times more permeable than their hemichannels and four times more permeable than Cx30 gap junctions. This suggests a significant physiological difference in the functions of Cx26 and Cx30 gap junctions in organs where they are co-expressed, at least with regard to the distribution of energy resources of the cells. It also demonstrates that the permeability characteristics of hemichannels can significantly diverge from that of their gap junctions for some connexins but not others.
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影响因子：
13.6
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.1616061113
发表时间：
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影响因子：
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作者：
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DOI：
10.1016/s0006-291x(03)00868-4
发表时间：
2003-06-13
影响因子：
3.1
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