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

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(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，并受多胺等内部阳离子粒子的电压依赖性通道阻断的调节。在本研究中，我们研究了Kir2家族经典的强内向整流钾通道的多胺阻断。新的发现如下：(1)Kir2.1和Kir2.2电流都被解释为通过对精胺阻滞剂敏感性不同的两个导体的电流之和，外向电流主要由对低亲和力阻滞剂敏感的小电导介导。精胺阻滞剂诱导的Kir2.2电流的内向整流比Kir2.1电流强，这是因为Kir2.2对低亲和力阻断敏感的分数电导比Kir2.1小，而Kir2.2对阻断的敏感性更大。(2)降低外部[K^+]使Kir2.1通道高、低亲和力阻断的电压依赖关系与K+平衡电位的移动平行。(3)当Kir2.1突变体孔壁上的负电荷残基被相应的未带电残基取代时，跨膜孔内的突变使Kir2.1几乎所有的电导都只对低亲和力阻断敏感，而细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通道表现出与内部阳离子颗粒阻断机制不同的内部pH敏感门控。

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.