| one publication added to basket [238740] | Up- and down-regulation of the mechano-gated K2P channel TREK-1 by PIP2 and other membrane phospholipids
Chemin, J.; Patel, A.J.; Duprat, F.; Sachs, F.; Lazdunski, M.; Honoré, E. (2007). Up- and down-regulation of the mechano-gated K2P channel TREK-1 by PIP2 and other membrane phospholipids. Pflügers Arch. Eur. J. Physiol. 455(1): 97-103. http://dx.doi.org/10.1007/s00424-007-0250-2
In: Pflügers Archiv - European Journal of Physiology. Springer: Berlin. ISSN 0031-6768; e-ISSN 1432-2013, more
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| Authors | | Top |
- Chemin, J.
- Patel, A.J.
- Duprat, F.
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- Sachs, F.
- Lazdunski, M.
- Honoré, E., more
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| Abstract |
TREK-1 is an unconventional K+ channel that is activated by both physical and chemical stimuli. In this study, we show that the inner leaflet membrane phospholipids, including PIP2, exert a mixed stimulatory and inhibitory effect on TREK-1. Intra-cellular phospholipids inhibit basal channel activity and activation by membrane stretch, intra-cellular acidosis and arachidonic acid. However, binding of endogenous negative inner leaflet phospholipids with poly-lysine reduces inhibition and reveals channel stimulation by exogenous intra-cellular phospholipids. A similar effect is observed with PI, PE, PS and PA, unlike DG, demonstrating that the phosphate at position 3 is required although the global charge of the molecule is not critical. Inhibition depends on the distal C-terminal domain that conditions channel mechano-sensitivity, but is independent of the positively charged PIP2 stimulatory site in the proximal C-terminal domain. This is, to our knowledge, the first report of an ion channel dually regulated by membrane phospholipids. |
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