A study on the regulation of the inward rectifier potassium current by polyamine.

多胺调节内向整流钾电流的研究

• 批准号: 17590188
• 负责人: YANAGI Keiko
• 金额: $ 1.92万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590188/
• 关键词: Ion channel; Potassium channel; Inward rectifier potassium current; Polyamine; Kir2; カリウムイオンチャネル

The classical strong inward rectifier K+ current plays a pivotal role in polarizing the membranes of excitable cells (cardiac myocytes and skeletal muscle fibers) and nonexcitable cells (e.g. smooth muscle cells, vascular endothelial cells and exocrine cells), and is regulated by voltage-dependent channel block by internal cationic particles, such as polyamines. In this study, we studied the polyamine block of the classical strong inward rectifier K+ channels in the Kir2 family. The new findings are as follows.( 1 ) The Kir2.1 and Kir2.2 currents are both explained as the sum of those through two conductances that differ in their susceptibility to the spermine block and the outward currents are mediated mostly by the small conductance susceptible to the low-affinity block. The inward rectification of Kir2.2 currents induced by the spermine block was stronger than that of Kir2.1 currents because the fractional conductance susceptible to the low-affinity block is smaller in Kir2.2 than in Kir2.1, and the susceptibility to block is greater in Kir2.2.( 2 ) Reducing external [K^+] shifted the voltage dependences of both the high-and low-affinity block of Kir2.1 channel in parallel with the shift in the equilibrium potential for K^+.( 3 ) When Kir2.1 mutants in which the negatively charged residues on the wall of the pore were substituted with corresponding uncharged residues, the mutation within the transmembrane pore made virtually all of the Kir2.1 conductance susceptible only to the low-affinity block, whereas the mutation in the cytoplasmic pore significantly reduced the susceptibility to low-affinity block.( 4 ) Kir2.1 channel exhibits an internal pH sensitive gating that is different from the mechanism of the block by internal cationic particles.

经典的强内向整流钾电流在可兴奋细胞（心肌细胞和骨骼肌纤维）和不可兴奋细胞（例如平滑肌细胞、血管内皮细胞和外分泌细胞）的膜极化中起关键作用，并且通过内部阳离子颗粒（如多胺）的电压依赖性通道阻断来调节。在这项研究中，我们研究了多胺阻断经典的强内向整流钾通道的Kir2家庭。新的调查结果如下。（1）Kir2.1和Kir2.2电流都被解释为通过两个电导的电流之和，这两个电导对精胺阻断的敏感性不同，外向电流主要由对低亲和力阻断敏感的小电导介导。由精胺阻断诱导的Kir2.2电流的内向整流比Kir2.1电流的内向整流强，因为Kir2.2中对低亲和力阻断敏感的电导分数比Kir2.1中小，并且Kir2.2中对阻断的敏感性更大。（2）降低外部[K^+]使Kir2.1通道的高亲和性和低亲和性阻断的电压依赖性发生了移动，与K^+平衡电位的移动平行。（3）当Kir2.1突变体中孔壁上的带负电荷的残基被相应的不带电荷的残基取代时，跨膜孔内的突变使得几乎所有的Kir2.1电导仅对低亲和力阻断敏感，而胞质孔内的突变显著降低了对低亲和力阻断的敏感性。（4）Kir2.1通道具有内部pH敏感性门控，与内部阳离子颗粒的阻断机制不同。