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Role of H5 domain in determining pore diameter and ion permeation through cyclic nucleotide-gated channels

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Abstract

ION permeation through membrane channels is thought to be governed by a narrow region of the channel pore termed the selectivity filter1, which has been proposed to discriminate among ions by both specific binding and molecular sieving, as determined by pore diameter. Recent evidence suggests that a conserved domain (known as H5, P or SS1-SS2) in voltage-gated potassium2–8, sodium9–13 and calcium 12channels contributes to the lining of the pore. Here we investigate whether the H5 domain determines pore diameter and examine the role of pore diameter in controlling ion permeation. These studies rely on differences in single channel conductance, ion selectivity and apparent pore diameter between cyclic nucleotide-gated channels cloned from bovine retina14 and catfish olfactory neurons15. Using chimaeric retinal–olfactory channels, we find that the H5 domain determines these differences in permeation properties, providing structural evidence that the cyclic nucleotide-gated channels are indeed members of the voltage-gated channel family15–17. Moreover, these results show directly that the H5 domain helps form the selectivity filter and that molecular sieving is important in controlling ion permeation.

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Authors and Affiliations

  1. Center for Neurobiology and Behavior, Columbia University, 722 West 168 Street, New York, New York, 10032, USA

    Evan H. Goulding, Gareth R. Tibbs, David Liu & Steven A. Siegelbaum

  2. Department of Physiology, Columbia University, 722 West 168 Street, New York, New York, 10032, USA

    Evan H. Goulding

  3. Department of Pharmacology, Columbia University, 722 West 168 Street, New York, New York, 10032, USA

    Steven A. Siegelbaum

  4. Howard Hughes Medical Institute, Columbia University, 722 West 168 Street, New York, New York, 10032, USA

    Gareth R. Tibbs & Steven A. Siegelbaum

Authors
  1. Evan H. Goulding
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  2. Gareth R. Tibbs
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  3. David Liu
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  4. Steven A. Siegelbaum
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Goulding, E., Tibbs, G., Liu, D. et al. Role of H5 domain in determining pore diameter and ion permeation through cyclic nucleotide-gated channels. Nature 364, 61–64 (1993). https://doi.org/10.1038/364061a0

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  • DOI: https://doi.org/10.1038/364061a0

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