A limited access compartment between the pore domain and cytosolic domain of the BK channel

Zhe Zhang, Yu Zhou, Jiu Ping Ding, Xiao Ming Xia, Christopher J. Lingle

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Cytosolic N-terminal segments of many K+ channel subunits mediate rapid blockade of ion permeation by physical occlusion of the ion-conducting pore. For some channels with large cytosolic structures, access to the channel pore by inactivation domains may occur through lateral entry pathways or "side portals" that separate the pore domain and associated cytosolic structures covering the axis of the permeation pathway. However, the extent to which side portals control access of molecules to the channel or influence channel gating is unknown. Here we use removal of inactivation by trypsin as a tool to examine basic residue accessibility in both the N terminus of the native auxiliary β2 subunit of Ca 2+-activated, BK-type K+ channels and β2 subunits with artificial inactivating N termini. The results show that, for BK channels, side portals define a protected space that precedes the channel permeation pathway and excludes small proteins such as trypsin but allows inactivation domains to enter. When channels are closed, inactivation domains readily pass through side portals, with a central antechamber preceding the permeation pathway occupied by an inactivation domain approximately half of the time under resting conditions. The restricted volume of the pathway through side portals is likely to influence kinetic properties of inactivation mechanisms, blockade by large pharmacological probes, and accessibility of modulatory factors to surfaces of the channel within the protected space.

Original languageEnglish
Pages (from-to)11833-11843
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number46
DOIs
StatePublished - Nov 15 2006

Keywords

  • Auxiliary β subunits
  • BK channels
  • Channel structure
  • Inactivation mechanisms
  • Patch clamp
  • Trypsin accessibility

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