Different tonic selectivities for connexins 26 and 32 produce rectifying gap junction channels
Different tonic selectivities for connexins 26 and 32 produce rectifying gap junction channels
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DOI：
10.1016/s0006-3495(99)77129-8
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发表时间：
1999-12-01
影响因子：
3.4
通讯作者：
Nicholson, BJ
中科院分区：
文献类型：
--
作者：
Suchyna, TM;Nitsche, JM;Nicholson, BJ
由大量连接蛋白同种型产生的间隙连接细胞间通道的功能多样性通过该家族成员之间的异型相互作用而显著增加。这在Cx 26/Cx 32异型通道的整流行为中特别明显（Barrio等人，1991. Proc. Natl. Acad. Sci. USA. 88：8410-8414）。在转染的小鼠神经母细胞瘤2A（N2 A）细胞中测定负责产生观察到的Cx 26/Cx 32异型间隙连接通道的整流电流的通道特性。转染子显示在120 mM KCl中Cx 26的最大单位电导（γ（j））为135 pS，Cx 32同型通道的最大单位电导（γ（j））为53 pS。谷氨酸盐对Cl的阴离子取代表明Cx 26通道以2.6：1的比例有利于阳离子，而Cx 32通道相对于电荷是非选择性的。在Cx 26/Cx 32异型细胞对中，电流-电压关系的宏观快速整流在单通道水平上通过整流γ（j）得到充分解释，当跨接电压（Vi）从-100 mV变为+100 mV时，Cx 26细胞作为正极，整流γ（j）增加2.9倍。基于离子浓度的Nemst-Planck方程和结内电势的Poisson方程，建立了离子通过差距结孔的电扩散模型。选择性特征归因于每个半通道，其基于孔隙特征（被视为沿半通道的长度沿着均匀）或每个连接蛋白特有的入口效应。分析GHK近似和完整的数值解预测Cx 32/Cx 26异型通道的整流特性，虽然没有充分的经验。该模型预测，在半通道的电导率/渗透性特性（也铸造为唐南电位）的不对称性将产生通道内的离子的积累或耗尽，这取决于电压极性，这将导致整流。
The functional diversity of gap junction intercellular channels arising from the large number of connexin isoforms is significantly increased by heterotypic interactions between members of this family. This is particularly evident in the rectifying behavior of Cx26/Cx32 heterotypic channels (Barrio et at., 1991. Proc. Natl. Acad. Sci. USA. 88:8410-8414). The channel properties responsible for producing the rectifying current observed for Cx26/Cx32 heterotypic gap junction channels were determined in transfected mouse neuroblastoma 2A (N2A) cells, Transfectants revealed maximum unitary conductances (gamma(j)) of 135 pS for Cx26 and 53 pS for Cx32 homotypic channels in 120 mM KCI. Anionic substitution of glutamate for CI indicated that Cx26 channels favored cations by 2.6:1, whereas Cx32 channels were relatively nonselective with respect to charge. In Cx26/Cx32 heterotypic cell pairs, the macroscopic fast rectification of the current-voltage relationship was fully explained at the single-channel level by a rectifying gamma(j) that increased by a factor of 2.9 as the transjunctional voltage (Vi) changed from -100 to +100 mV with the Cx26 cell as the positive pole. A model of electrodiffusion of ions through the gap junction pore based on Nemst-Planck equations for ion concentrations and the Poisson equation for the electrical potential within the junction is developed. Selectivity characteristics ave ascribed to each hemichannel based on either pore features (treated as uniform along the length of the hemichannel) or entrance effects unique to each connexin. Both analytical GHK approximations and full numerical solutions predict rectifying characteristics for Cx32/Cx26 heterotypic channels, although not to the full extent seen empirically. The model predicts that asymmetries in the conductance/permeability properties of the hemichannels (also cast as Donnan potentials) will produce either an accumulation or a depletion of ions within the channel, depending on voltage polarity, that will result in rectification.