lmmol · Proteins

Potassium channel subfamily K member 2

UniProt O95069 Organism Homo sapiens Gene KCNK2, TREK, TREK1

Also known as: KCNK2, TREK, TREK1

Function

K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate. Converts to voltage-independent 'leak' conductance mode upon stimulation by various stimuli including mechanical membrane stretch, acidic pH, heat and lipids. Reversibly converts between a voltage-insensitive K(+) 'leak' channel and a voltage-dependent outward rectifying K(+) channel in a phosphorylation-dependent manner (By similarity). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (By similarity). In trigeminal ganglia sensory neurons, the heterodimer of KCNK2/TREK-1 and KCNK18/TRESK inhibits neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). At trigeminal A-beta afferent nerves, the heterodimer of KCNK2/TREK-1 and KCNK4/TRAAK is mostly coexpressed at nodes of Ranvier where it conducts voltage-independent mechanosensitive and thermosensitive currents, allowing rapid action potential repolarization, high speed and high frequence saltatory conduction on myelinated nerves to ensure prompt sensory responses (By similarity). In hippocampal astrocytes, the heterodimer of KCNK2/TREK-1 and KCNK1/TWIK-1 allows passive K(+) conductance under basal conditions, but changes ion selectivity and becomes permeable to L-glutamate and Cl(-) ions upon binding to G protein subunit GNG4 in stimulated astrocytes. Mediates rapid L-glutamate release in response to activation of G protein-coupled receptors, such as F2R and CNR1 (By similarity). In hippocampal pyramidal neurons, the homodimer of KCNK2/TREK-1 contributes to gamma-aminobutyric acid (GABA) B-induced slow inhibitory postsynaptic potential. Associates with AKAP5 and Gs-protein-coupled receptor B2AR at postsynaptic dense bodies and converts to a leak channel no longer sensitive to stimulation by arachidonic acid, acidic pH or mechanical stress, nor inhibited by Gq-coupled receptors but still under the negative control of Gs-coupled receptors (By similarity). Permeable to other monovalent cations such as Rb(+) and Cs(+) (By similarity).

Classification

Family (Pfam)
PF07885 Ion_trans_2
InterPro
2pore_dom_K_chnl, 2pore_dom_K_chnl_TREK, K_chnl_dom
Functional cluster
Membrane Transporters & GPCRs

Experimental structures · PDB · 1

A predicted model is available from AlphaFold.

Gene Ontology · 38

Drugs targeting this protein · 5

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 11 cited papers

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