Polyvalent cations constitute the voltage gating particle in human connexin37 hemichannels.
Polyvalent cations constitute the voltage gating particle in human connexin37 hemichannels.
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DOI：
10.1085/jgp.200409023
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发表时间：
2004-11
期刊：
影响因子：
--
通讯作者：
Hanck DA
中科院分区：
文献类型：
--
作者：
Puljung MC;Berthoud VM;Beyer EC;Hanck DA
连接蛋白寡聚形成细胞间通道，在电压和化学试剂(如二价阳离子)的作用下门控。从历史上看，这被认为是两个独立的过程。这里，人类连接蛋白37(HCx37)半通道的数据表明，电压门控可以解释为阻断/非阻断，而不需要独立的电压门。HCx37半通道在负电位下关闭，在正电位下以时间依赖的方式开放。然而，在没有多价阳离子的情况下，通道在相对负的电位下打开，电流相对于电压呈线性传递。在浴液中加入多价阳离子，可以浓度依赖的方式抑制负电位下的电流。抑制可以解释为hCx37的电压依赖性阻断，电场直接作用于多价阳离子，驱使它们通过孔洞到达细胞内的位置。在正电位下，在多价阳离子存在的情况下，电场有利于多价离子从细胞内阻断部位外流，从而允许电流流动。电流的出现速度取决于浴液中多价阳离子的种类和价态。复极化时电流衰减的速度取决于浴液中多价阳离子的浓度，这与多价块的失活一致，并且很快(时间常数为数十毫秒)，这意味着多价离子在通道孔内或附近有很高的局部浓度。持续的去极化以一种与通量、电压和时间无关的方式减缓了失活。HCx37电压门控作为多价阻断/非阻断的模型可以扩展到解释文献中关于hCx37间隙结沟道行为的观察。
Connexins oligomerize to form intercellular channels that gate in response to voltage and chemical agents such as divalent cations. Historically, these are believed to be two independent processes. Here, data for human connexin37 (hCx37) hemichannels indicate that voltage gating can be explained as block/unblock without the necessity for an independent voltage gate. hCx37 hemichannels closed at negative potentials and opened in a time-dependent fashion at positive potentials. In the absence of polyvalent cations, however, the channels were open at relatively negative potentials, passing current linearly with respect to voltage. Current at negative potentials could be inhibited in a concentration-dependent manner by the addition of polyvalent cations to the bathing solution. Inhibition could be explained as voltage-dependent block of hCx37, with the field acting directly on polyvalent cations, driving them through the pore to an intracellular site. At positive potentials, in the presence of polyvalent cations, the field favored polyvalent efflux from the intracellular blocking site, allowing current flow. The rate of appearance of current depended on the species and valence of the polyvalent cation in the bathing solution. The rate of current decay upon repolarization depended on the concentration of polyvalent cations in the bathing solution, consistent with deactivation by polyvalent block, and was rapid (time constants of tens of milliseconds), implying a high local concentration of polyvalents in or near the channel pore. Sustained depolarization slowed deactivation in a flux-dependent, voltage- and time-independent fashion. The model for hCx37 voltage gating as polyvalent block/unblock can be expanded to account for observations in the literature regarding hCx37 gap junction channel behavior.
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DOI：
10.1073/pnas.79.10.3188
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BAUD, C;KADO, RT;MARCHER, K
通讯作者：
MARCHER, K
影响因子：
3.4
作者：
Banach, K;Ramanan, SV;Brink, PR
通讯作者：
Brink, PR
DOI：
10.1006/bbrc.2000.4121
发表时间：
2001-01-19
影响因子：
3.1
作者：
Kumari, SS;Varadaraj, K;Brink, PR
通讯作者：
Brink, PR
影响因子：
4.5
作者：
Pfahnl, A;Dahl, G
通讯作者：
Dahl, G
影响因子：
3.8
作者：
Ebihara, L;Steiner, E
通讯作者：
Steiner, E