The potassium channel subunit Kvβ3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials
The potassium channel subunit Kvβ3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials
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DOI：
10.1111/j.1742-4658.2009.07334.x
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发表时间：
2009-11-01
期刊：
影响因子：
5.4
通讯作者：
Dermietzel, Rolf
中科院分区：
文献类型：
--
作者：
Bunse, Stefanie;Locovei, Silviu;Dermietzel, Rolf
Pannexin 1 (Panx1) 是脊椎动物中发现的第二个间隙连接蛋白家族的成员，似乎优先形成非连接膜通道。 Panx1 的候选调节蛋白是钾通道亚基 Kv beta 3，之前通过细菌双杂交策略鉴定出。在这里，我们通过免疫沉淀报告了 Panx1 与 Kv beta 3 在神经母细胞瘤细胞系 (Neuro2A) 中共表达时的物理关联。此外，Panx1 和 Kv beta 3 的体内共表达发生在小鼠海马和小脑中。已知 Kv beta 3 在还原条件下可加速钾通道的失活，否则钾通道会缓慢失活。我们随后发现，当暴露于还原剂时，Panx1 通道电流表现出显着降低，并且这种效应在 Kv beta 3 存在时减弱。显然，Kv beta 3 参与调节 Panx1 通道对氧化还原电位的敏感性。此外，当 Kv beta 3 共表达时，Panx1 通道阻滞剂甘诺索隆和丙磺舒抑制 Panx1 电流的效果较差。 Kv beta 3 对 Panx1 的影响是通过相互作用蛋白质调节 Panx1 通道功能的第一个例子，并表明感知氧化还原电位变化的生理重要性。
Pannexin 1 (Panx1), a member of the second gap junction protein family identified in vertebrates, appears to preferentially form non-junctional membrane channels. A candidate regulatory protein of Panx1 is the potassium channel subunit Kv beta 3, previously identified by bacterial two-hybrid strategies. Here, we report on the physical association of Panx1 with Kv beta 3 by immunoprecipitation when co-expressed in a neuroblastoma cell line (Neuro2A). Furthermore, in vivo co-expression of Panx1 and Kv beta 3 was shown to occur in murine hippocampus and cerebellum. Kv beta 3 is known to accelerate inactivation of otherwise slowly inactivating potassium channels under reducing conditions. We subsequently found that Panx1 channel currents exhibit a significant reduction when exposed to reducing agents, and that this effect is attenuated in the presence of Kv beta 3. Apparently, Kv beta 3 is involved in regulating the susceptibility of Panx1 channels to redox potential. Furthermore, the Panx1 channel blockers carbenoxolone and Probenecid were less effective in inhibiting Panx1 currents when Kv beta 3 was co-expressed. The influence of Kv beta 3 on Panx1 is the first example of modulation of Panx1 channel function(s) by interacting proteins, and suggests the physiological importance of sensing changes in redox potentials.