Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.
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.
Oliver
Dominik
D
Institute of Physiology, University of Freiburg, Hermann-Herder-Strabetae 7, 79104 Freiburg, Germany.
Lien
Cheng-Chang
CC
Soom
Malle
M
Baukrowitz
Thomas
T
Jonas
Peter
P
Fakler
Bernd
B
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000502:physiology; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004537:Eicosanoic Acids / Q000378:metabolism* / Q000494:pharmacology; D063388:Endocannabinoids; D007395:Interneurons / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism* / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010539:Permeability; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism* / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014981:Xenopus
D001095:Arachidonic Acids; D002412:Cations; D051668:Delayed Rectifier Potassium Channels; D004537:Eicosanoic Acids; D063388:Endocannabinoids; D008563:Membrane Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011994:Recombinant Proteins; D011107:Polylysine; C078814:anandamide