title: Role of H5 domain in determining pore diameter and ion permeation through cyclic nucleotide-gated channels.
abstract: Ion permeation through membrane channels is thought to be governed by a narrow region of the channel pore termed the selectivity filter, 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 potassium, sodium and calcium channels 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 retina and catfish olfactory neurons. 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 family. Moreover, these results show directly that the H5 domain helps form the selectivity filter and that molecular sieving is important in controlling ion permeation.
authors.affiliation: Department of Physiology, Columbia University, New York, New York 10032.
authors.forename: E H
authors.initials: EH
authors.lastname: Goulding
authors.forename: G R
authors.initials: GR
authors.lastname: Tibbs
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: S A
authors.initials: SA
authors.lastname: Siegelbaum
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002397:Catfishes; D002417:Cattle; D002463:Cell Membrane Permeability; D003001:Cloning, Molecular; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009832:Olfactory Nerve / Q000378:metabolism; D009865:Oocytes; D011188:Potassium / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014981:Xenopus
chemical_list: D007473:Ion Channels; D011993:Recombinant Fusion Proteins; D012964:Sodium; D011188:Potassium; D002118:Calcium