TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family.
Recently, several mammalian K(+) channel subunits (TWIK, TREK-1, TRAAK, and TASK) possessing four transmembrane segments and two pore-forming domains have been identified. We report the cloning of a new member of this tandem-pore K(+) channel from a rat cerebellum cDNA library. It is a 538-amino acid protein and shares 65% amino acid sequence identity with TREK-1. Therefore, the new clone was named TREK-2. Unlike TREK-1, whose mRNA has been reported to be expressed in many different tissues, TREK-2 mRNA is expressed mainly in the cerebellum, spleen, and testis as judged by reverse transcriptase-polymerase chain reaction and Northern blot analysis. Expression of TREK-2 in COS-7 cells induced a time-independent and non-inactivating K(+)-selective current. TREK-2 was partially blocked (36%) by 2 mm Ba(2+). In symmetrical 150 mm KCl, the single-channel conductances were 110 picosiemens at -40 mV and 68 picosiemens at +40 mV, and the mean open time was 0.9 ms at -40 mV. TREK-2 was activated by membrane stretch or acidic pH. At -40 mm Hg pressure, channel activity increased 10-fold above the basal level. TREK-2 was also activated by arachidonic acid and other naturally occurring unsaturated free fatty acids. These results show that TREK-2 is a new member of the tandem-pore K(+) channel family and belongs to the class of mechanosensitive and fatty acid-stimulated K(+) channels.
Bang
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Department of Physiology and Biophysics, Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois 60064, USA.
Kim
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Kim
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002531:Cerebellum / Q000378:metabolism*; D003001:Cloning, Molecular; D015723:Gene Library; D006031:Glycosylation; D008564:Membrane Potentials / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain; D011189:Potassium Chloride / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C503444:Kcnk10 protein, rat; C503434:Kcnk4 protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D011994:Recombinant Proteins; C103742:potassium channel protein TREK-1; D011189:Potassium Chloride