title: Reversible oxidation of myometrial voltage-gated potassium channels with hydrogen peroxide.
abstract: The uteri, spontaneously active or Ca(2+) (6 mM) induced, were allowed to equilibrate, and to inhibit voltage-gated potassium (K(V)) channels 1 mM 4-amino pyridine (4-AP) was applied for 15 min before adding H(2)O(2). H(2)O(2) was added cumulatively: 2 μM, 20 μM, 200 μM, 400 μM, and 3 mM. Average time for H(2)O(2) concentrations (2, 20, 200, and 400) μM to reach its full effect was 15 min. H(2)O(2) 3 mM had a prolonged effect and therefore was left to act for 30 min. Two-way ANOVA showed significant differences in time dependency between spontaneous and Ca(2+)-induced rat uteri after applying 3 mM H(2)O(2) (type of contraction, P = 0.0280), but not 400 μM H(2)O(2) (P = 0.9271). Our results indicate that H(2)O(2) oxidises channel intracellular thiol groups and activates the channel, inducing relaxation. Cell antioxidative defence system quickly activates glutathione peroxidase (GSHPx) defence mechanism but not catalase (CAT) defence mechanism. Intracellular redox mechanisms repair the oxidised sites and again establish deactivation of K(V) channels, recuperating contractility. In conclusion, our results demonstrate that K(V) channels can be altered in a time-dependent manner by reversible redox-dependent intracellular alterations.
authors.affiliation: Department of Physiology, Institute for Biological Research Sinisa Stankovic, University of Belgrade, 11000 Belgrade, Serbia. kuabena@yahoo.com
authors.forename: Isabella
authors.initials: I
authors.lastname: Appiah
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Nikolic-Kokic
authors.forename: Zorana
authors.initials: Z
authors.lastname: Orescanin-Dusic
authors.forename: Ratko
authors.initials: R
authors.lastname: Radojicic
authors.forename: Slobodan
authors.initials: S
authors.lastname: Milovanovic
authors.forename: Mihajlo
authors.initials: M
authors.lastname: Spasic
authors.forename: Dusko
authors.initials: D
authors.lastname: Blagojevic
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: D000975:Antioxidants; D024642:Potassium Channels, Voltage-Gated; D006861:Hydrogen Peroxide