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TREK-1 is a mechanosensitive member of the two-pore domain potassium channel family (2PK+) that is also sensitive to lipids, free fatty acids (including arachidonic acid), temperature, intracellular pH, and a range of clinically relevant compounds including volatile anaesthetics. TREK-1 is known to be expressed at high levels in excitable tissues, such as the nervous system, the heart and smooth muscle, where it is believed to play a prominent role in controlling resting cell membrane potential and electrical excitability. In this report, we use RT-PCR, Western blotting and immunohistochemistry to confirm that human derived osteoblasts and MG63 cells express TREK-1 mRNA and protein. In addition, we show gene expression of TREK2c and TRAAK channels. Furthermore, whole cell patch clamp electrophysiology demonstrates that these cells express a spontaneously active, outwardly rectifying potassium "background leak" current that shares many similarities to TREK-1. The outward current is largely insensitive to TEA and Ba2+, and is sensitive to application of lysophosphatidylcholine (LPC). In addition, blocking TREK-1 channel activity is shown to upregulate bone cell proliferation. It is concluded that human osteoblasts functionally express TREK-1 and that these channels contribute, at least in part, to the resting membrane potential of human osteoblast cells. We hypothesise a possible role for TREK-1 in mechanotransduction, leading to bone remodelling.

Original publication

DOI

10.1002/jcp.20536

Type

Journal article

Journal

J Cell Physiol

Publication Date

03/2006

Volume

206

Pages

738 - 748

Keywords

Adolescent, Adult, Animals, COS Cells, Cell Proliferation, Cercopithecus aethiops, Child, Humans, Immunohistochemistry, Lysophosphatidylcholines, Membrane Potentials, Middle Aged, Osteoblasts, Polymerase Chain Reaction, Potassium Channel Blockers, Potassium Channels, Tandem Pore Domain, Transfection