Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids Journal Article


Author(s): Oliver, Dominik; Lien, Cheng-Chang; Soom, Malle; Baukrowitz, Thomas; Jonas, Peter; Fakler, Bernd
Article Title: Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids
Affiliation
Abstract: Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct alpha and beta subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.
Keywords: Animals; Kinetics; Protein Structure, Tertiary; Signal Transduction; Patch-Clamp Techniques; Cell Membrane/metabolism; Xenopus; Brain/physiology; Cations; Delayed Rectifier Potassium Channels; Interneurons/physiology; Ion Channel Gating/drug effects; Membrane Lipids/*metabolism/pharmacology; Oocytes; Permeability; Polylysine/pharmacology; Polyunsaturated Alkamides; Potassium Channels/chemistry/*metabolism/physiology; Protein Subunits; Recombinant Proteins/chemistry/metabolism; Arachidonic Acids/metabolism/pharmacology; Eicosanoic Acids/metabolism/pharmacology; Phosphatidylinositol 4,5-Diphosphate/metabolism/pharmacology; Potassium Channels, Voltage-Gated/antagonists & inhibitors/chemistry/metabolism/physiology
Journal Title: Science
Volume: 304
Issue 5668
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Publication Place: United States
Date Published: 2004-01-01
Start Page: 265
End Page: 70
DOI: 10.1126/science.1094113
Open access: no