Kondo C, Repunte V P, Satoh E, Yamada M, Horio Y, Matsuzawa Y, Pott L, Kurachi Y
Department of Pharmacology II, Osaka University, Japan.
Recept Channels. 1998;6(2):129-40.
The ATP-sensitive K+ (KATP) channels, e.g. in heart and pancreatic beta-cells, open spontaneously in the absence of intracellular ATP (ATPi). Their unitary conductance is approximately 80 pS with 150 mM extracellular K+. These features are shared by the K+ channels composed of various sulfonylurea receptors (SURs) and Kir6.2, whereas SUR/Kir6.1 channels have a smaller conductance (approximately 35 pS) and do not open spontaneously in the absence of ATPi. To identify the structural elements in Kir6.0 subunits which determine these properties, we analyzed the properties of functional K+ channels composed of SUR2A, the cardiac type SUR, and various chimeras of Kir6.1 and Kir6.2 heterologously expressed in HEK (human embryonic kidney) 293T cells. The analyses indicate that the extracellular linker domain between the two putative membrane-spanning regions is responsible for the difference in the single channel conductance between SUR2A/Kir6.1 and SUR2A/Kir6.2 channels. The cytosolic N-terminal domain of Kir6.2 was mandatory for spontaneous channel opening in the absence of ATPi, although a part of C-terminus was also involved. These results implicate specific regions of Kir6.0 in the spontaneous opening and the single channel conductance.
ATP敏感性钾离子（KATP）通道，例如存在于心脏和胰腺β细胞中的通道，在细胞内ATP（ATPi）缺失时会自发开放。在细胞外钾离子浓度为150 mM时，其单通道电导约为80 pS。由各种磺脲类受体（SURs）和Kir6.2组成的钾离子通道也具有这些特性，而SUR/Kir6.1通道的电导较小（约35 pS），并且在没有ATPi的情况下不会自发开放。为了确定Kir6.0亚基中决定这些特性的结构元件，我们分析了由心脏型SUR即SUR2A与Kir6.1和Kir6.2的各种嵌合体在人胚肾（HEK）293T细胞中异源表达所构成的功能性钾离子通道的特性。分析表明，两个假定跨膜区域之间的细胞外环连域是SUR2A/Kir6.1和SUR2A/Kir6.2通道单通道电导差异的原因。Kir6.2的胞质N端结构域是在没有ATPi时通道自发开放所必需的，尽管C端的一部分也有参与。这些结果表明Kir6.0的特定区域与自发开放和单通道电导有关。
