title: Membrane microdomain determines the specificity of receptor-mediated modulation of Kv7/M potassium currents.
abstract: The Kv7/M current is one of the major mechanisms controlling neuronal excitability, which can be modulated by activation of the G protein-coupled receptor (GPCR) via distinct signaling pathways. Membrane microdomains known as lipid rafts have been implicated in the specificity of various cell signaling pathways. The aim of this study was to understand the role of lipid rafts in the specificity of Kv7/M current modulation by activation of GPCR. Methyl-β-cyclodextrin (MβCD), often used to disrupt the integrity of lipid rafts, significantly reduced the bradykinin receptor (B2R)-induced but not muscarinic receptor (M1R)-induced inhibition of the Kv7/M current. B2R and related signaling molecules but not M1R were found in caveolin-containing raft fractions of the rat superior cervical ganglia. Furthermore, activation of B2R resulted in translocation of additional B2R into the lipid rafts, which was not observed for the activation of M1R. The increase of B2R-induced intracellular Ca(2+) was also greatly reduced after MβCD treatment. Finally, B2R but not M1R was found to interact with the IP3 receptor. In conclusion, the present study implicates an important role for lipid rafts in mediating specificity for GPCR-mediated inhibition of the Kv7/M current.
authors.affiliation: The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, Hebei Province, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei Province, China; Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.forename: X
authors.initials: X
authors.lastname: Du
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051656:KCNQ Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D021962:Membrane Microdomains / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000502:physiology*; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D051656:KCNQ Potassium Channels; D026902:Potassium Channel Blockers; D043643:Receptor, Muscarinic M1; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin
keywords: 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid; 50% effective concentration; B(2)R; BK; DRG; EC(50); EDTA; EGTA; G protein-coupled receptor; G(q) protein-coupled membrane receptors; G(q)PCRs; GPCR; HEPES; Kv7/M current; MR; MβCD; NGF; Oxo-M; PIP2; RT; SCG; TBS; Tris-buffered saline; bradykinin; bradykinin receptor; dorsal root ganglion; ethylene glycol tetraacetic acid; ethylenediaminetetraacetic acid; lipid raft; methyl-β-cyclodextrin; modulation; muscarinic receptor; nerve growth factor; oxotremorine-M; phosphatidylinositol 4,5-bisphosphate; receptor; room temperature; specificity; superior cervical ganglia