Linker-gating ring complex as passive spring and Ca(2+)-dependent machine for a voltage- and Ca(2+)-activated potassium channel

Neuron. 2004 Jun 10;42(5):745-56. doi: 10.1016/j.neuron.2004.05.001.

Abstract

Ion channels are proteins that control the flux of ions across cell membranes by opening and closing (gating) their pores. It has been proposed that channels gated by internal agonists have an intracellular gating ring that extracts free energy from agonist binding to open the gates using linkers that directly connect the gating ring to the gates. Here we find for a voltage- and Ca(2+)-activated K+ (BK) channel that shortening the linkers increases channel activity and lengthening the linkers decreases channel activity, both in the presence and absence of intracellular Ca2+. These observations are consistent with a mechanical model in which the linker-gating ring complex forms a passive spring that applies force to the gates in the absence of Ca2+ to modulate the voltage-dependent gating. Adding Ca2+ then changes the force to further activate the channel. Both the passive and Ca(2+)-induced forces contribute to the gating of the channel.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Cloning, Molecular / methods
  • Dose-Response Relationship, Drug
  • Electric Conductivity
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Humans
  • Ion Channel Gating / physiology
  • Kidney
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Models, Biological
  • Mutation / physiology
  • Oocytes
  • Patch-Clamp Techniques / methods
  • Potassium Channels, Calcium-Activated / chemistry*
  • Potassium Channels, Calcium-Activated / metabolism
  • Potassium Channels, Voltage-Gated / chemistry*
  • Potassium Channels, Voltage-Gated / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary / physiology*
  • Transfection / methods
  • Xenopus

Substances

  • Potassium Channels, Calcium-Activated
  • Potassium Channels, Voltage-Gated
  • Calcium