KCNK2 Membrane Protein Introduction

Introduction of KCNK2

KCNK2, the full name is potassium channel subfamily K member 2, also known as outward rectifying potassium channel protein TREK-1, TREK-1 K(+) channel subunit, two-pore domain potassium channel TREK-1, two-pore potassium channel TPKC1. KCNK2 is a member of the two-hole potassium (K2P) channel family. Human KCNK2 is highly expressed in the brain and is particularly abundant in interstitial neurons containing GABA (γ-aminobutyric acid) of the caudate nucleus and putamen. KCNK2 is also expressed in the prefrontal cortex, hippocampus, hypothalamus, midbrain serotonergic neurons of the dorsal raphe nucleus and sensory neurons of dorsal root ganglia (DRG). KCNK2 is also present in peripheral tissues such as gastrointestinal tracts. KCNK2 is a signal integrator that responds to a variety of physiological and pathological inputs.

Function of KCNK2 Membrane Protein

KCNK2 has complex gating and regulation by membrane receptors and second messengers and is central to ischemic and epileptic neuroprotection, pain perception and depression. In addition, KCNK2 is opened by neuroprotective agents, volatile and gaseous anesthetics, whereas it is inhibited by clinical doses of antidepressants, suggesting that the channel is an important pharmacological target. KCNK2 activity is stimulated by membrane stretching, heat, intracellular acidosis, and cellular lipids. Therefore, KCNK2 is qualified as a polymodal sensory ion channel that integrates a variety of physical and chemical stimuli. The C-terminal domain of this channel plays a major role in transducing of these stimuli into the channel opening. The proposed model suggests that the tight dynamic interaction of this domain with the inner leaflets of the plasma membrane is central to the mechanism of channel gating and regulation by membrane receptors and second messenger pathways.

Fig.1 Space-filling model of TREK-1 viewed from the cytosolic side. (Renigunta, 2015)

Application of KCNK2 Membrane Protein in Literature

1. Lugenbiel P., et al. TREK-1 (K2P2.1) K+ channels are suppressed in patients with atrial fibrillation and heart failure and provide therapeutic targets for rhythm control. Basic Res Cardiol. 2017, 112(1):8. PubMed ID: 28005193
   
   

   Decreased atrial TREK-1 expression in atrial fibrillation patients with severe heart failure was verified in this article.

2. Tomuschat C., et al. Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung's disease. Pediatr Res. 2016, 80(5):729-733. PubMed ID: 27384506
   
   

   The decreased TREK-1 expression in the ganglia and ganglion intestine observed in Hirschsprung's disease (HSCR) may alter intestinal epithelial barrier function, leading to the development of enterocolitis.

3. Zhang M., et al. Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest. Acta Pharmacol Sin. 2016, 37(9):1190-8. PubMed ID: 27397543
   
   

   TREK-1 overexpression inhibited CHO cell proliferation by inhibiting the activity of the PKA and p38/MAPK signaling pathways and subsequently inducing G1 phase cell arrest.

4. Huang H., et al. Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrier function. Cell Mol Immunol. 2016, 13(1):110-8. PubMed ID: 25683610
   
   

   The expression of TREK1 was a benefit to restore intestinal epithelial barrier function in an allergic environment.

5. Zhang G.M., et al. Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer. Oncotarget. 2015, 6(21):18460-8. PubMed ID: 25962960
   
   

   The data suggested that potassium channel protein TREK-1 (TREK-1) might be a biomarker in castration resistance free survival (CRFS) judgment of prostate cancer (PCa), as well as a potential therapeutic target.

KCNK2 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms or other protein forms in the same family. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-KCNK2 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Renigunta V, et al. (2015). Much more than a leak: structure and function of K2P-channels. Pflugers Arch-Eur J Physiol. 467:867–894.

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