Lu Z, MacKinnon R
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Nature. 1994 Sep 15;371(6494):243-6. doi: 10.1038/371243a0.
Inward-rectifier potassium channels conduct K+ across the cell membrane more efficiently in the inward than outward direction. This unusual conduction property is directly related to the biological action of these channels. One basis for inward rectification is voltage-dependent blockade by intracellular Mg2+ (refs 1, 7-9): strong inward-rectifier channels are so sensitive to intracellular Mg2+ that no outward K+ current is measurable under physiological conditions; weak inward rectifiers are less sensitive and allow some K+ to flow outwards. Background K1 channels and acetylcholine-regulated K+ channels from the heart are examples of strong inward rectifiers and ATP-sensitive K+ channels are weak rectifiers. Here we show that mutations at one position in the second transmembrane segment can alter the Mg2+ affinity and convert a weakly rectifying channel (ROMK1) into a strong rectifier. The amino acid at this position exposes its side chain to the aqueous pore and affects Mg2+ blockade as well as K+ conduction through an electrostatic mechanism.
内向整流钾通道在细胞膜上介导K⁺内流的效率高于外流。这种不同寻常的传导特性与这些通道的生物学作用直接相关。内向整流的一个基础是细胞内Mg²⁺的电压依赖性阻断（参考文献1、7 - 9）：强内向整流通道对细胞内Mg²⁺非常敏感，以至于在生理条件下无法检测到外向K⁺电流；弱内向整流通道敏感性较低，允许一些K⁺外流。心脏中的背景K⁺通道和乙酰胆碱调节的K⁺通道是强内向整流通道的例子，而ATP敏感性K⁺通道是弱整流通道。在这里我们表明，第二个跨膜片段中一个位置的突变可以改变Mg²⁺亲和力，并将一个弱整流通道（ROMK1）转变为强整流通道。该位置的氨基酸将其侧链暴露于水相孔中，并通过静电机制影响Mg²⁺阻断以及K⁺传导。
