title: Induction of a fast inactivation gating on delayed rectifier Shab K(+) channels by the anti-inflammatory drug celecoxib.
abstract: Celecoxib is a drug designed to selectively inhibit COX-2, an inflammation-inducible cyclooxygenase isoform, over the constitutively expressed COX-1 isoform. In addition to this selective inhibition it is now known that celecoxib exerts a variety of effects on several types of ion channels, thus producing secondary physiological effects. In this work we demonstrate that at therapeutically relevant concentrations celecoxib interacts with Shab K(+) channels specifically promoting a fast inactivation gating (without blocking the pore or significantly affecting other gating processes). At least two celecoxib molecules bind to each channel promoting a fast inactivation that develops from both open and closed states. Channel inactivation in turn causes a reduction of the size of I(K). Taken together, our observations show that in addition to its intended therapeutic target celecoxib is a useful tool to further study the mechanism of Shab channel inactivation.
authors.affiliation: Departamento de Fisiología, Universidad Nacional Autónoma de México, DF México.
authors.forename: Imilla I
authors.initials: II
authors.lastname: Arias-Olguin
authors.forename: Elisa
authors.initials: E
authors.lastname: Carrillo
authors.forename: Bernardo
authors.initials: B
authors.lastname: Meza-Torres
authors.forename: Carolina
authors.initials: C
authors.lastname: Barriga-Montoya
authors.forename: Daniel
authors.initials: D
authors.lastname: Balleza
authors.forename: Froylan
authors.initials: F
authors.lastname: Gomez-Lagunas
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D000068579:Celecoxib; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism*; D011485:Protein Binding; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D051669:Shab Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011994:Recombinant Proteins; D051669:Shab Potassium Channels; D013449:Sulfonamides; D000068579:Celecoxib; D011188:Potassium