Chimeras of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K+ channels.
Chimeras of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K+ channels.
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Kir6.1 和 Kir6.2 的嵌合体揭示了参与 ATP 敏感 K 通道自发开放和统一电导的结构元件。
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Y. Kurachi
中科院分区：
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作者：
C. Kondo;V. P. Repunte;E. Satoh;M. Yamada;Y. Horio;Yuji Matsuzawa;L. Pott;Y. Kurachi
在没有细胞内三磷酸腺苷(ATPI)的情况下，ATP敏感的K+(KATP)通道，例如心脏和胰岛的β细胞，会自发开放。它们的单位电导约为80ps，胞外K+为150 mM。这些特征被各种磺脲受体(SURS)和Kir6.2组成的K+通道所共有，而SuR/Kir6.1通道的电导较小(约35pS)，在没有ATPI的情况下不会自发开放。为了确定决定这些特性的Kir6.0亚基中的结构元件，我们分析了在HEK(人胚胎肾)293T细胞中异源表达的由SUR2A、心脏型SUR和各种Kir6.1和Kir6.2嵌合体组成的功能性K+通道的特性。分析表明，SUR2A/Kir6.1和SUR2A/Kir6.2通道的单通道电导差异是由SUR2A/Kir6.1和SUR2A/Kir6.2两个跨膜区之间的胞外连接结构域引起的。在没有ATPI的情况下，Kir6.2的胞浆N-末端结构域对于自发开放通道是必需的，尽管也有部分C-末端参与。这些结果暗示了Kir6.0在自发开放和单通道电导中的特定区域。
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.