KCNK2

Function in neurons

TREK-1 is part of the subfamily of mechano-gated potassium channels that are present in mammalian neurons. They can be gated in both chemical and physical ways and can be opened via both physical stimuli and chemical stimuli. TREK-1 channels are found in a variety of tissues, but are particularly abundant in the brain and heart and are seen in various types of neurons. The C-terminal of TREK-1 channels plays a role in the mechanosensitivity of the channels.

In the neurons of the central nervous system, TREK-1 channels are important in physiological, pathophysiological, and pharmacological processes, including having a role in electrogenesis, ischemia, and anesthesia. TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal cord ischemia and is being evaluated as a potential target for new developments of therapeutic agents for neurology and anesthesiology.

In the absence of a properly functioning cytoskeleton, TREK-1 channels can still open via mechanical gating. The cell membrane functions independently of the cytoskeleton and the thickness and curvature of the membrane is able to modulate the activity of the TREK-1 channels. The change in thickness is thought to be sensed by an amphipathic helix that extends from the inner leaflet of the membrane.

The insertion of certain compounds into the membrane, including inhaled anesthetics and propofol, activate TREK-1 through the enzyme phospholipase D2 (PLD2). Prior to the addition of anesthetic, PLD2 associates with GM-1 lipid rafts. After anesthetic, the enzyme or a complex of the enzyme and the channel traffic to PIP2 domains where the enzyme makes phosphatidic acid that opens the channel.

References

References

1. (Oct 1998). "Mapping of human potassium channel genes TREK-1 (KCNK2) and TASK (KCNK3) to chromosomes 1q41 and 2p23". Genomics.
2. (Dec 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews.
3. "Entrez Gene: KCNK2 potassium channel, subfamily K, member 2".
4. (1996). "Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel". The EMBO Journal.
5. (1998). "A mammalian two pore domain mechano-gated S-like K+ channel". The EMBO Journal.
6. (1992). "Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1". Journal of Immunology.
7. (2001). "Lipid and mechano-gated 2P domain K(+) channels". Current Opinion in Cell Biology.
8. (2018). "A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force". Social Science Research Network.
9. (28 May 2020). "Studies on the mechanism of general anesthesia.". Proceedings of the National Academy of Sciences of the United States of America.