title: Oxidation of NADPH on Kvbeta1 inhibits ball-and-chain type inactivation by restraining the chain.
abstract: The Kv1 family voltage-dependent K(+) channels assemble with cytosolic β subunits (Kvβ), which are composed of a flexible N terminus followed by a structured core domain. The N terminus of certain Kvβs inactivates the channel by blocking the ion conduction pore, and the core domain is a functional enzyme that uses NADPH as a cofactor. Oxidation of the Kvβ-bound NADPH inhibits inactivation and potentiates channel current, but the mechanism behind this effect is unknown. Here we show that after oxidation, the core domain binds to part of the N terminus, thus restraining it from blocking the channel. The interaction is partially mediated by two negatively charged residues on the core domain and three positively charged ones on the N terminus. These results provide a molecular basis for the coupling between the cellular redox state and channel activity, and establish Kvβ as a target for pharmacological control of Kv1 channels.
authors: Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors: Yaping
authors: Y
authors: Pan
authors: Jun
authors: J
authors: Weng
authors: Elena J
authors: EJ
authors: Levin
authors: Ming
authors: M
authors: Zhou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004594:Electrophysiology; D005822:Genetic Vectors; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D051381:Rats; D017422:Sequence Analysis, DNA; D013050:Spectrometry, Fluorescence
chemical_list: D017931:DNA Primers; D051662:Kv1.1 Potassium Channel; D009249:NADP