Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel.
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.
Lu
Z
Z
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
MacKinnon
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002462:Cell Membrane; D002478:Cells, Cultured; D004563:Electrochemistry; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008274:Magnesium / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D014981:Xenopus
D005971:Glutamates; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid; D008274:Magnesium