Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel.
We have cloned human TREK-1, one of the newly emerging mammalian family of 2-P domain potassium channels. The channel has 411 amino acids with a 41-amino-acid extension at the C-terminus when compared with the cloned mouse TREK-1 channel. Expression of hTREK-1 produced a substantial hyperpolarising shift in resting membrane potential accompanied by the induction of large, outwardly rectifying, non-inactivating currents which were potassium selective. Pharmacologically, hTREK-1-mediated currents were only blocked to a limited extent by classic potassium channel blockers or open channel pore blockers known to potently inhibit other channels. The channel was reversibly potentiated by arachidonic acid. CNS distribution of hTREK-1 is widespread with higher levels being observed in caudate, putamen, amygdala, thalamus and spinal cord. Only low levels of expression were seen in the majority of peripheral regions. Thus, hTREK-1, although functionally and pharmacologically similar to mouse TREK-1, appears to have a more CNS-specific distribution.
Meadows
H J
HJ
Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Helen_J_Meadows@sbphrd.com
Benham
C D
CD
Cairns
W
W
Gloger
I
I
Jennings
C
C
Medhurst
A D
AD
Murdock
P
P
Chapman
C G
CG
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D014018:Tissue Distribution; D014982:Xenopus laevis / Q000378:metabolism
D010446:Peptide Fragments; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1