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Ion conduction pore is conserved among potassium channels

Nature volume 413, pages 809–813 (2001)Cite this article

Abstract

Potassium channels, a group of specialized membrane proteins, enable K+ ions to flow selectively across cell membranes. Transmembrane K+ currents underlie electrical signalling in neurons and other excitable cells. The atomic structure of a bacterial K+ channel pore has been solved by means of X-ray crystallography. To the extent that the prokaryotic pore is representative of other K+ channels, this landmark achievement has profound implications for our general understanding of K+ channels. But serious doubts have been raised concerning whether the prokaryotic K+ channel pore does actually represent those of eukaryotes. Here we have addressed this fundamental issue by substituting the prokaryotic pore into eukaryotic voltage-gated and inward-rectifier K+ channels. The resulting chimaeras retain the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among K+ channels.

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Figure 1: Replacement of the Shaker pore module with that of KcsA.
Figure 2: Triple mutation in the P-loop renders KcsA–Shaker channels sensitive to AgTx2.
Figure 3: Effects of extracellular K+ concentration and a G104A mutation on the gating of KcsA–Shaker.
Figure 4: Deletion of a segment in the P-loop of the IRK1 channel.
Figure 5: Substitution of the KcsA pore in IRK1.
Figure 6: Mutation T107D renders KcsA–Shaker inwardly rectifying.

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Acknowledgements

We thank P. De Weer for review and discussion of our manuscript; C. M. Armstrong, R. MacKinnon and K. J. Swartz for discussions and suggestions; R. MacKinnon and E. Perozo for KcsA cDNA; K. J. Swartz for Shaker-IR cDNA subcloned in the pGEM–HESS vector; L. Y. Jan for IRK1 cDNA; and J. Yang for IRK1 cDNA subcloned in the pGEM–HESS vector. This study was supported by the National Institute of General Medical Sciences. Z.L. is the recipient of an Independent Scientist Award from the National Heart, Lung and Blood Institute.

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  1. Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, 19104, Pennsylvania, USA

    Zhe Lu, Angela M. Klem & Yajamana Ramu

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Correspondence to Zhe Lu.

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Lu, Z., Klem, A. & Ramu, Y. Ion conduction pore is conserved among potassium channels. Nature 413, 809–813 (2001). https://doi.org/10.1038/35101535

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