Calcium-dependent gating of MthK, a prokaryotic potassium channel

Brittany Zadek1, Crina M Nimigean

  • 1Department of Biochemistry and Membrane Biology, University of California, Davis, 95616, USA.

Insights

Calcium-gated MthK potassium channels exhibit distinct slow and fast gating modes influenced by calcium and voltage. Millimolar calcium significantly increases opening frequency, revealing strong coupling for channel activation.

Area of Science:

  • Molecular biology
  • Biophysics
  • Ion channel function

Background:

  • MthK is a prokaryotic potassium channel, structurally relevant to eukaryotic Ca(2+)-dependent channels.
  • Limited functional data exists for MthK, hindering understanding of its gating mechanisms.

Purpose of the Study:

  • To characterize the gating properties of MthK at the single-channel level.
  • To elucidate the mechanism of calcium (Ca2+) activation in MthK channels.
  • To investigate the influence of voltage on MthK gating.

Main Methods:

  • Single-channel electrophysiology.
  • Detailed kinetic analysis of MthK gating.
  • Application of a modified Monod-Wyman-Changeux (MWC) model.

Main Results:

  • MthK displays two gating modes: slow (Ca2+-dependent) and fast (voltage-dependent).
  • Millimolar Ca2+ enhances MthK open probability >100-fold by increasing opening frequency.
  • Ca2+ dose-response shows a high Hill coefficient (n≈8), indicating strong Ca2+-binding and channel-opening coupling.
  • Depolarization reduces fast gating flickers and increases slow gate opening probability.

Conclusions:

  • MthK gating is modulated by both Ca2+ and voltage through distinct mechanisms.
  • The study provides mechanistic insights into Ca2+ activation and voltage effects on MthK.
  • A modified MWC model successfully captures MthK's mechanistic gating features.

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