MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating
MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating
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DOI：
10.1074/jbc.m310501200
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发表时间：
2004-02-27
影响因子：
4.8
通讯作者：
Abbott, GW
中科院分区：
文献类型：
--
作者：
Lewis, A;McCrossan, ZA;Abbott, GW
哺乳动物神经元的高频放电需要由Kv3.1和Kv3.2钾通道α亚基的同源或异源组装体产生的超快速延迟整流钾电流。Kv3.1 α亚基也可以通过与MinK相关肽2（MiRP 2）（一种单一跨膜结构域钾通道辅助亚基）共组装形成较慢的激活通道。在这里，使用从大鼠克隆和表达在中国仓鼠卵巢细胞中的通道亚基，我们表明，由MinK，MiRP 1和MiRP 2的调制是一个一般的机制，减缓Kv3.1和Kv3.2通道的激活和失活和加速失活，创造一个功能多样的通道复合物。MiRP 1还负移Kv3.1和Kv3.2通道激活的电压依赖性。此外，MinK、MiRP 1和MiRP 2各自形成具有Kv3.1-Kv3.2异聚体的通道，所述异聚体在动力学上彼此不同并且与MiRP/同聚Kv 3通道不同。这些发现说明了Kv3.1和Kv3.2钾电流的功能库的动态扩展机制，并建议这些α亚基在持续快速神经元放电范围外的作用。
High frequency firing in mammalian neurons requires ultra-rapid delayed rectifier potassium currents generated by homomeric or heteromeric assemblies of Kv3.1 and Kv3.2 potassium channel alpha subunits. Kv3.1 alpha subunits can also form slower activating channels by coassembling with MinK-related peptide 2 (MiRP2), a single transmembrane domain potassium channel ancillary subunit. Here, using channel subunits cloned from rat and expressed in Chinese hamster ovary cells, we show that modulation by MinK, MiRP1, and MiRP2 is a general mechanism for slowing of Kv3.1 and Kv3.2 channel activation and deactivation and acceleration of inactivation, creating a functionally diverse range of channel complexes. MiRP1 also negatively shifts the voltage dependence of Kv3.1 and Kv3.2 channel activation. Furthermore, MinK, MiRP1, and MiRP2 each form channels with Kv3.1-Kv3.2 heteromers that are kinetically distinct from one another and from MiRP/homomeric Kv3 channels. The findings illustrate a mechanism for dynamic expansion of the functional repertoire of Kv3.1 and Kv3.2 potassium currents and suggest roles for these alpha subunits outside the scope of sustained rapid neuronal firing.