The potassium channels Kv2.1 and Kv2.2 are widely expressed throughout the mammalian brain. Kv2.1 provides the majority of delayed rectifying current in rat hippocampus while both channels are differentially expressed in cortex. Particularly unusual is their neuronal surface localization pattern: while half the channel population is freely-diffusive on the plasma membrane as expected from the generalized Singer & Nicolson fluid mosaic model, the other half localizes into micron-sized clusters on the soma, dendrites, and axon initial segment. These clusters contain hundreds of channels, which for Kv2.1, are largely non-conducting. Competing theories of the mechanism underlying Kv2.1 clustering have included static tethering to being corralled by an actin fence. Now, recent work has demonstrated channel clustering is due to formation of endoplasmic reticulum/plasma membrane (ER/PM) junctions through interaction with ER-resident VAMP-associated proteins (VAPs). Interaction between surface Kv2 channels and ER VAPs groups channels together in clusters. ER/PM junctions play important roles in inter-organelle communication: they regulate ion flux, are involved in lipid transfer, and are sites of endo- and exocytosis. Kv2-induced ER/PM junctions are regulated through phosphorylation of the channel C-terminus which in turn regulates VAP binding, providing a rapid means to create or dismantle these microdomains. In addition, insults such as hypoxia or ischemia disrupt this interaction resulting in ER/PM junction disassembly. Kv2 channels are the only known plasma membrane protein to form regulated, injury sensitive junctions in this manner. Furthermore, it is likely that concentrated VAPs at these microdomains sequester additional interactors whose functions are not yet fully understood.

钾通道Kv2.1和Kv2.2在整个哺乳动物脑中广泛表达。Kv2.1在大鼠海马中提供了大多数延迟整流电流，而两个通道在皮质中差异表达。它们的神经元表面定位模式尤其不寻常：虽然一半的通道种群可以像广义Singer＆Nicolson流体镶嵌模型所预期的那样在质膜上自由扩散，但是另一半则位于体，树突和轴突初始段。这些群集包含数百个通道，对于Kv2.1，这些通道基本上是不导电的。有关Kv2.1群集机制的竞争理论包括静态束缚以被肌动蛋白围栏所破坏。现在，最近的工作表明，通道聚类是由于与ER驻留VAMP相关蛋白（VAP）相互作用而形成内质网/质膜（ER / PM）连接。表面Kv2通道和ER VAP之间的交互将通道集中在一起。ER / PM连接在细胞间通讯中起重要作用：它们调节离子通量，参与脂质转移，并且是内吞和胞吐作用的部位。Kv2诱导的ER / PM连接通过通道C末端的磷酸化来调节，进而调节VAP结合，从而提供了创建或拆除这些微区的快速方法。另外，诸如缺氧或局部缺血之类的侮辱破坏了这种相互作用，导致ER / PM接头拆卸。Kv2通道是唯一已知的形成受调节的质膜蛋白，以这种方式伤害敏感的路口。此外，在这些微域中集中的VAP可能会隔离其功能尚未完全了解的其他相互作用子。