KCNK10 Membrane Protein Introduction

Introduction of KCNK10

Potassium channel subfamily K member 10 (KCNK10), also known as outward rectifying potassium channel protein TREK-2, which is a eukaryotic mechanosensitive ion channel belonging to the two-pore-domain (K2P) family of K+-selective channels. The structure of KCNK10 is characterized by four transmembrane helices (M1-M4), an extracellular cap domain and a pseudo-tetrameric architecture around the central selectivity filter, which is responsible for the regulation of physical factors and pharmacological agents, such as natural ligands including polyunsaturated fatty acids (arachidonic acid (AA)), volatile anesthetics, neuroprotective drugs and antidepressants (fluoxetine), etc. It is notable that the gating of KCNK10-formed K+ channels occurs primarily within or near the selectivity filter selective uptake, where the conduction pathway remains open even in the functionally closed channel. However, the many other K+ channels have a classical helix bundle-crossing gate which allows the entrance via constriction of the cytoplasmic entrance to the pore. KCNK10 is expressed extensively in the central and peripheral nervous system, especially in primary afferent neurons in the dorsal root ganglion (DRG), where it is involved in determining the resting membrane potential and excitability of these cells.

Basic Information of KCNK10
Protein Name Potassium channel subfamily K member 10
Gene Name KCNK10
Aliases TREK-2
Organism Homo sapiens (Human)
UniProt ID P57789
Transmembrane Times 4
Length (aa) 538

Function of KCNK10 Membrane Protein

As a member of K2P family, KCNK10 plays an important role in the generation of leak currents which are important modulators of neuronal activity. It is documented that KCNK10 underlies a wide range of important physiological processes, such as touch, hearing, balance, the sensation of pain, and the regulation of blood pressure and other fundamental processes such as osmotic homeostasis. Along with the related TREK-1 and TRAAK channels, KCNK10 can exhibit mechanosensitivity, meaning that KCNK10 is regulated by a wide range of other biological, chemical, and physical stimuli, such as intracellular (pHi) and extracellular pH (pHext), membrane stretch, voltage, temperature, lipids, and polyunsaturated fatty acids, various GPCR-coupled signaling pathways, and a wide range of clinically relevant drugs. Such “polymodal” regulation allows KCNK10 to participate in many different signaling pathways to control membrane excitability, significantly in some populations of sensory neurons for the sensation of pain. In the heart, activation of KCNK10 by membrane stretch allows it to couple mechanical forces to alternations in membrane potential, which is thought to contribute to the stretch-activated potassium currents involved in mechano-electrical coupling and arrhythmogenesis.

Model of K2P channel gating and inhibition by norfluoxetine. Fig.1 Model of K2P channel gating and inhibition by norfluoxetine. (Dong, 2015)

Application of KCNK10 Membrane Protein in Literature

  1. Nematian-Ardestani E., et al. The effects of stretch activation on ionic selectivity of the TREK-2 K2P K+ channel. Channels. 2017, 11(5): 482-486. PubMed ID: 28723241

    In this article, the authors demonstrated that the KCNJ8-formed mechanosensitive K+ channel responded to changes in membrane tension by undergoing a major structural change from its ‘down’ state to the more expanded ‘up’ state conformation without a loss of K+ selectivity.

  2. Aryal P., et al. Bilayer-mediated structural transitions control mechanosensitivity of the TREK-2 K2P channel. Structure. 2017, 25(5): 708-718. e2. PubMed ID: 28392258

    This article used molecular dynamics simulations to examine the role of KCNK10 in a lipid bilayer, showing that TREK-2 moved from the “down” to “up” conformation in direct response to membrane stretch. They also examined the role of the transmembrane pressure profile in this process.

  3. McClenaghan C., et al. Polymodal activation of the TREK-2 K2P channel produces structurally distinct open states. The Journal of general physiology. 2016, 147(6): 497-505. PubMed ID: 27241700

    This article used the state-dependent TREK-2 inhibitor norfluoxetine to reconcile these previously contradictory gating models that the activation of K+ channels induced more than one structurally distinct open state. The stimulus of pressure, temperature, voltage, and pH produce did not simply cause switching between the up and down conformations.

  4. Lolicato M., et al. Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K2P channels. Neuron. 2014, 84(6): 1198-1212. PubMed ID: 25500157

    The authors reported the structures of K2P4.1 (TRAAK) bearing C-type gate-activating mutations that revealed a tilting and straightening of the M4 inner transmembrane helix and buckling of the M2 transmembrane helix and uncovered a unique aspect of K2P modulation.

  5. Haenisch S., et al. miRNA-187-3p-mediated regulation of the KCNK10/TREK-2 potassium channel in a rat epilepsy model. ACS chemical neuroscience. 2016, 7(11): 1585-1594. PubMed ID: 27609046

    The authors confirmed the regulation of miRNA-187-3p and revealed that KCNK10/TREK-2 upregulation might serve a protective function with a beneficial impact on astrocytic potassium and glutamate homeostasis.

KCNK10 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-KCNK10 antibody development services.

Over years, Creative Biolabs has successfully generated many functional membrane proteins for our customers. We are happy to tailor one-stop, custom-oriented service packages regarding a variety of membrane protein targets. Please feel free to contact us for more information.


  1. Dong Y Y, et al. (2015). K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science. 347(6227): 1256-1259.

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