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.

Authors and Affiliations

1. Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, CM19 5AW, UK

   H.J. Meadows, C.D. Benham, C. Jennings & A.D. Medhurst

2. Biotechnology and Genetics, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, CM19 5AW, UK

   W. Cairns, I. Gloger, P. Murdock & C.G. Chapman

Received after revision: 30 November 1999

Electronic Publication

Reprints and permissions