title: Ionic interactions of Ba2+ blockades in the MthK K+ channel.
abstract: The movement and interaction of multiple ions passing through in single file underlie various fundamental K(+) channel properties, from the effective conduction of K(+) ions to channel blockade by Ba(2+) ions. In this study, we used single-channel electrophysiology and x-ray crystallography to probe the interactions of Ba(2+) with permeant ions within the ion conduction pathway of the MthK K(+) channel. We found that, as typical of K(+) channels, the MthK channel was blocked by Ba(2+) at the internal side, and the Ba(2+)-blocking effect was enhanced by external K(+). We also obtained crystal structures of the MthK K(+) channel pore in both Ba(2+)-Na(+) and Ba(2+)-K(+) environments. In the Ba(2+)-Na(+) environment, we found that a single Ba(2+) ion remained bound in the selectivity filter, preferably at site 2, whereas in the Ba(2+)-K(+) environment, Ba(2+) ions were predominantly distributed between sites 3 and 4. These ionic configurations are remarkably consistent with the functional studies and identify a molecular basis for Ba(2+) blockade of K(+) channels.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou 310058, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hengjun
authors.initials: H
authors.lastname: Cui
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou 310058, China sye@zju.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
mesh_terms: D019843:Archaeal Proteins / Q000187:drug effects* / Q000378:metabolism*; D001464:Barium / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019843:Archaeal Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D001464:Barium; D012964:Sodium; D011188:Potassium