Chavez R A, Gray A T, Zhao B B, Kindler C H, Mazurek M J, Mehta Y, Forsayeth J R, Yost C S
Elan Pharmaceuticals, Menlo Park, California 94025, USA.
J Biol Chem. 1999 Mar 19;274(12):7887-92. doi: 10.1074/jbc.274.12.7887.
Potassium channels are found in all mammalian cell types, and they perform many distinct functions in both excitable and non-excitable cells. These functions are subserved by several different families of potassium channels distinguishable by primary sequence features as well as by physiological characteristics. Of these families, the tandem pore domain potassium channels are a new and distinct class, primarily distinguished by the presence of two pore-forming domains within a single polypeptide chain. We have cloned a new member of this family, TWIK-2, from a human brain cDNA library. Primary sequence analysis of TWIK-2 shows that it is most closely related to TWIK-1, especially in the pore-forming domains. Northern blot analysis reveals the expression of TWIK-2 in all human tissues assayed except skeletal muscle. Human TWIK-2 expressed heterologously in Xenopus oocytes is a non-inactivating weak inward rectifier with channel properties similar to TWIK-1. Pharmacologically, TWIK-2 channels are distinct from TWIK-1 channels in their response to quinidine, quinine, and barium. TWIK-2 is inhibited by intracellular, but not extracellular, acidification. This new clone reveals the existence of a subfamily in the tandem pore domain potassium channel family with weak inward rectification properties.
钾通道存在于所有哺乳动物细胞类型中，并且它们在可兴奋细胞和非可兴奋细胞中发挥许多不同的功能。这些功能由几个不同的钾通道家族来承担，这些家族可通过一级序列特征以及生理特性来区分。在这些家族中，串联孔结构域钾通道是一个新的独特类别，主要通过在单个多肽链中存在两个孔形成结构域来区分。我们从人脑cDNA文库中克隆了这个家族的一个新成员TWIK - 2。TWIK - 2的一级序列分析表明，它与TWIK - 1关系最为密切，尤其是在孔形成结构域。Northern印迹分析显示，TWIK - 2在除骨骼肌外的所有检测的人体组织中均有表达。在非洲爪蟾卵母细胞中异源表达的人TWIK - 2是一种非失活的弱内向整流器，其通道特性与TWIK - 1相似。在药理学上，TWIK - 2通道在对奎尼丁、奎宁和钡的反应方面与TWIK - 1通道不同。TWIK - 2受到细胞内酸化而非细胞外酸化的抑制。这个新克隆揭示了串联孔结构域钾通道家族中存在一个具有弱内向整流特性的亚家族。
