Lipids and two-pore domain K+ channels in excitable cells.
Two-pore domain potassium channels (2PK) make up the newest branch of the potassium channel super-family. The channels are time- and voltage-independent and carry leak or "background" currents that are regulated by many different signaling molecules. These currents play an important role in setting the resting membrane potential and excitability of excitable cells, and, as a consequence, modulation of 2PK channel activity is thought to underlie the function of physiological processes as diverse as the sedation of anesthesia, regulation of normal cardiac rhythm and synaptic plasticity associated with simple forms of learning. Lipids, including arachidonate and its lipoxygenase metabolites, platelet-activating factor and anandamide have been identified as important mediators of some 2PK channels. Regulation can be effected by several different mechanisms. Some channels are regulated by G-protein-coupled receptors using well described signaling pathways that terminate in the activation of protein kinase C, whereas others are modulated by the direct interaction of the lipid with the channel.
Besana
Alessandra
A
Center for Molecular Therapeutics, Department of Pharmacology, Columbia University, 630 W168th Street, New York, NY 10032, USA.
Robinson
Richard B
RB
Feinmark
Steven J
SJ
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D063388:Endocannabinoids; D006352:Heart Ventricles / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008568:Memory; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D009435:Synaptic Transmission; D013997:Time Factors
D001095:Arachidonic Acids; D063388:Endocannabinoids; D009419:Nerve Tissue Proteins; D010972:Platelet Activating Factor; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D016718:Arachidonic Acid; D008084:Lipoxygenase; C078814:anandamide