title: Cysteine oxidation and rundown of large-conductance Ca2+-dependent K+ channels.
abstract: 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.
authors.affiliation: Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104, USA. zgp480@gmail.com
authors.forename: Guangping
authors.initials: G
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hoshi
mesh_terms: D002118:Calcium / Q000008:administration & dosage*; D002460:Cell Line; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction
chemical_list: C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D003545:Cysteine; D002118:Calcium