Kubo Y
Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Japan.
Recept Channels. 1996;4(2):73-83.
It is known that the rectification property of the inward rectifier K+ channel, IRK1, is caused by a block of outward current by cytoplasmic Mg2+ and polyamines, and that the voltage dependence of rectification shifts according to the equilibrium potential of K+. Here it is shown that extracellular K+ (K+ o) but not intracellular K+ (K+ i) affects the activation kinetics of IRK1. A mutant in which the conserved positively charged residue arginine was replaced by a tyrosine (R148Y) exhibited slower activation and a negative shift of the conductance-voltage relationship. In addition, the conductance did not saturate at negative potentials as was observed for the wild type. When using T1+o instead of K+ o as permeant ion, the differences between the wild type and the mutant were qualitatively similar but less prominent. These results suggest that extracellular cations (e.g., K+ o or T1+ o) play a role in the activation of IRK1. Since the effects of K+ o or T1+ o were altered in the mutant, the site R148 presumably is involved in channel regulation by extracellular cations.
已知内向整流钾通道IRK1的整流特性是由胞质中的Mg2+和多胺对外向电流的阻断引起的，并且整流的电压依赖性会根据钾离子的平衡电位而发生变化。本文表明，细胞外钾离子（K+ o）而非细胞内钾离子（K+ i）会影响IRK1的激活动力学。一个保守的带正电荷残基精氨酸被酪氨酸取代的突变体（R148Y）表现出较慢的激活速度以及电导-电压关系的负向偏移。此外，在负电位下电导不像野生型那样达到饱和。当使用Tl+ o而非K+ o作为通透离子时，野生型和突变体之间的差异在性质上相似但不太明显。这些结果表明细胞外阳离子（例如，K+ o或Tl+ o）在IRK1的激活中起作用。由于K+ o或Tl+ o的作用在突变体中发生了改变，推测位点R148参与了细胞外阳离子对通道的调节。
