Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel

• Published in: Pflügers Archiv 2000-04, Vol.439 (6), p.714-722
• Main Authors: Meadows, H.J., Benham, C.D., Cairns, W., Gloger, I., Jennings, C., Medhurst, A.D., Murdock, P., Chapman, C.G.
• Format: Article
• Language: English
• Subjects: Cloning
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004249900235

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.[PUBLICATION ABSTRACT]