Cysteine oxidation and rundown of large-conductance Ca2+-dependent K+ channels

Biochem Biophys Res Commun. 2006 Apr 21;342(4):1389-95. doi: 10.1016/j.bbrc.2006.02.079. Epub 2006 Feb 23.


Gating of Slo1 calcium- and voltage-gated potassium (BK) channels involves allosteric interactions among the channel pore, voltage sensors, and Ca(2+)-binding domains. The allosteric activation of the Slo1 channel is in turn modulated by a variety of regulatory processes, including oxidation. Cysteine oxidation alters functional properties of Slo1 channels and has been suggested to contribute to the decrease in the channel activity following patch excision often referred to as rundown. This study examined the biophysical mechanism of rundown and whether oxidation of cysteine residues located in the C-terminus of the human Slo1 channel (C430 and C911) plays a role. Comparison of the changes in activation properties in different concentrations of Ca(2+) among the wild-type, C430A, and C911A channels during rundown and by treatment with the oxidant hydrogen peroxide showed that oxidation of C430 and C911 markedly contributes to the rundown process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / administration & dosage*
  • Cell Line
  • Cysteine / metabolism*
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Oxidation-Reduction


  • Kcnma1 protein, mouse
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Cysteine
  • Calcium