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Pore Structure of the Cys-loop Ligand-gated Ion Channels

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Abstract

The Cys-loop receptor family of ligand-gated ion channels (LGICs) play a key role in synaptic transmission in the central nervous system of animals. Recent advances have led to the elucidation of two crystal structures of related prokaryotic LGICs and the electron micrograph derived structure of the acetylcholine receptor from Torpedo marmorata. Here, we review the structural and biochemical data that form our understanding of the structure of the channel pore. We introduce original data from the glycine receptor using the substituted-cysteine accessibility technique and show that while the helical structure of the segment that surrounds the channel pore is generally agreed, the location of the channel gate, the pore diameter and the structure that forms the entry to the channel pore are likely to differ between receptors. The fundamental structural differences between anion and cation selective receptors and how these differences are related to the pore structure are also considered.

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Acknowledgments

We thank Kerrie Pierce, Anna Scimone, Cheryl Handford and Irene Michas for excellent technical assistance. This work was supported by the National Health and Medical Research Council of Australia (Project grants 230806 and 455310 and Research Fellowship 157209). N.L.A was the recipient of an Australian Postgraduate Award.

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Correspondence to Trevor M. Lewis.

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Absalom, N.L., Schofield, P.R. & Lewis, T.M. Pore Structure of the Cys-loop Ligand-gated Ion Channels. Neurochem Res 34, 1805–1815 (2009). https://doi.org/10.1007/s11064-009-9971-2

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