Tucker S J, Bond C T, Herson P, Pessia M, Adelman J P
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, Oregon 97201, USA.
J Biol Chem. 1996 Mar 8;271(10):5866-70. doi: 10.1074/jbc.271.10.5866.
Inwardly rectifying K+ channel subunits may form homomeric or heteromeric channels with distinct functional properties. Hyperpolarizing commands delivered to Xenopus oocytes expressing homomeric Kir 4.1 channels evoke inwardly rectifying K+ currents which activate rapidly and undergo a pronounced decay at more hyperpolarized potentials. In addition, Kir 4.1 subunits form heteromeric channels when coexpressed with several other inward rectifier subunits. However, coexpression of Kir 4.1 with Kir 3.4 causes an inhibition of the Kir 4.1 current. We have investigated this inhibitory effect and show that it is mediated by interactions between the predicted transmembrane domains of the two subunit classes. Other subunits within the Kir 3.0 family also exhibit this inhibitory effect which can be used to define subgroups of the inward rectifier family. Further, the mechanism of inhibition is likely due to the formation of an "inviable complex" which becomes degraded, rather than by formation of stable nonconductive heteromeric channels. These results provide insight into the assembly and regulation of inwardly rectifying K+ channels and the domains which define their interactions.
内向整流钾离子通道亚基可形成具有不同功能特性的同聚体或异聚体通道。向表达同聚体Kir 4.1通道的非洲爪蟾卵母细胞施加超极化指令会诱发内向整流钾离子电流，该电流迅速激活，并在更超极化的电位下发生明显衰减。此外，当Kir 4.1亚基与其他几个内向整流亚基共表达时，会形成异聚体通道。然而，Kir 4.1与Kir 3.4共表达会导致Kir 4.1电流受到抑制。我们研究了这种抑制作用，并表明它是由这两类亚基预测的跨膜结构域之间的相互作用介导的。Kir 3.0家族中的其他亚基也表现出这种抑制作用，可用于定义内向整流家族的亚组。此外，抑制机制可能是由于形成了一种会降解的“不可行复合物”，而不是形成稳定的非传导性异聚体通道。这些结果为深入了解内向整流钾离子通道的组装和调节以及定义其相互作用的结构域提供了线索。
