title: Molecular regulations governing TREK and TRAAK channel functions.
abstract: K+ channels with two-pore domain (K2p) form a large family of hyperpolarizing channels. They produce background currents that oppose membrane depolarization and cell excitability. They are involved in cellular mechanisms of apoptosis, vasodilatation, anesthesia, pain, neuroprotection and depression. This review focuses on TREK-1, TREK-2 and TRAAK channels subfamily and on the mechanisms that contribute to their molecular heterogeneity and functional regulations. Their molecular diversity is determined not only by the number of genes but also by alternative splicing and alternative initiation of translation. These channels are sensitive to a wide array of biophysical parameters that affect their activity such as unsaturated fatty acids, intra- and extracellular pH, membrane stretch, temperature, and intracellular signaling pathways. They interact with partner proteins that influence their activity and their plasma membrane expression. Molecular heterogeneity, regulatory mechanisms and protein partners are all expected to contribute to cell specific functions of TREK currents in many tissues.
authors.affiliation: Université de Nice Sophia Antipolis, UFR Sciences, Nice, France. noel@ipmc.cnrs.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sandoz
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
mesh_terms: D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010442:Peptide Chain Initiation, Translational / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005231:Fatty Acids, Unsaturated; C503438:KCNK10 protein, human; C503432:KCNK4 protein, human; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D020033:Protein Isoforms; C103742:potassium channel protein TREK-1