Cue to Exeunt

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Science  17 Jan 2003:
Vol. 299, Issue 5605, pp. 311
DOI: 10.1126/science.299.5605.311c

Many biological channels conduct ions with similar activities in both directions; however, a subset known as inward rectifier (IRK) channels conducts K+ ions into the cell more readily. This subset of channels helps to maintain the normal resting potential and also influences heart rate and neurotransmitter action (via G proteins). Rectification occurs because at voltages where K+ would normally flow outward, the channel is blocked by intracellular cations (Mg2+ or polyamines).

But why does this occur only in IRK channels? The answer comes from the 1.8 Å structure of the intracellular region of the G protein-gated IRK channel (GIRK1), solved by Nishida and MacKinnon. The tetrameric assembly contains a pore about 30 Å in length and 7 to 15 Å in diameter. Docking this cytoplasmic pore onto the narrower transmembrane piping of the MthK channel gives an ion conduction pathway roughly 60 Å in length. The pattern of negatively charged and hydrophobic amino acids lining the inner wall of the pore would attract complementary polyamines. The authors propose that the strong voltage dependence of inward rectification arises because, as a polyamine moves into the cytoplasmic pore, it herds and forcibly queues K+ ions toward the transmembrane exit. — VV

Cell111, 957 (2002).

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