IMIS | Flanders Marine Institute
 

Flanders Marine Institute

Platform for marine research

IMIS

Publications | Institutes | Persons | Datasets | Projects | Maps
[ report an error in this record ]basket (0): add | show Printer-friendly version

Regulation of the mechano-gated K2P channel TREK-1 by membrane phospholipids
Chemin, J.; Patel, A.J.; Delmas, P.; Sachs, F.; Lazdunski, M.; Honoré, E. (2007). Regulation of the mechano-gated K2P channel TREK-1 by membrane phospholipids. Curr. Top. Membr. 59: 155-170. hdl.handle.net/10.1016/S1063-5823(06)59007-6
In: Current Topics in Membranes. Academic Press: San Diego. ISSN 1063-5823, more
Peer reviewed article  

Available in Authors 

Authors  Top 
  • Chemin, J.
  • Patel, A.J.
  • Delmas, P.
  • Sachs, F.
  • Lazdunski, M.
  • Honoré, E., more

Abstract
    This chapter discusses the regulation of the mechano-gated K2P channel, TREK-1 by membrane phospholipids. TREK-1 (KCNK2 or K2P2.1) is a polymodal K+ channel that is activated by membrane stretch, intracellular acidosis, heat, and cellular lipids, such as arachidonic acid (AA). Phospholipids, including PIP2, exert a dual dose-dependent effect on TREK-1. Low concentrations transform the mechanogated K+ channel TREK-1 into a leak K+ channel. The phospholipid-sensing domain is a positively charged cluster in the proximal C-terminal domain. This region also encompasses the proton sensor E306 that is required for the activation of TREK-1 by cytosolic acidosis. Protonation of E306 increases channel-phospholipid interaction leading to TREK-1 opening without direct-mechanical stimulation. At higher concentrations, intracellular phospholipids inhibit channel activation by stretch, intracellular acidosis, and AA. Binding endogenous negative inner leaflet phospholipids with polylysine reduces the inhibition and reveals channel stimulation by exogenous intracellular phospholipids. Both stimulatory and inhibitory effects are observed with phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidic acid (PA), but not diacylglycerol (DG), suggesting that the phosphate at position 3 is required, although the net charge is not critical. Membrane phospholipids, including PIP2, are major regulators of TREK-1 channel activity.

All data in IMIS is subject to the VLIZ privacy policy Top | Authors