KCNK6 Membrane Protein Introduction

Introduction of KCNK6

KCNK6, the full name is potassium channel subfamily K member 6, also known as inward rectifying potassium channel protein TWIK-2, TWIK-originated similarity sequence. KCNK6 is the only member of the 2P domain K⁺ channel family to display a time-dependent inactivation at depolarized potentials. At physiological temperatures and even extreme depolarization potentials, KCNK6 is only partially inactivated and still has a steady current. Interestingly, the inactivation of KCNK6 is impaired under conditions rich in K⁺. KCNK6 is abundantly expressed in placenta, esophagus, stomach, salivary gland, spleen, and aorta. Furthermore, substantial expression of KCNK6 in the spleen, peripheral blood leukocytes, thymus, lymph nodes, and bone marrow suggest that KCNK6 is also a component of the immune system K⁺ channel library. Thus, KCNK6 can constitute an interesting pharmacological target for the control of immunoreactivity and smooth muscle tone. Full-length KCNK6 and splice variants have the same expression pattern in most of the tissues. However, in the colon, fetal heart, atria, and atrioventricular node, splice variants were not significantly expressed, while the full-length form is abundant.

Function of KCNK6 Membrane Protein

KCNK6 has unique biophysical, pharmacological and regulatory properties in the 2P domain K⁺ channel family. Inhalation of anesthetics can block the KCNK6 channel. In the case of external acidosis (pH 6.4), KCNK6 activity decreased by only 36%. KCNK6 is slightly potentiated by the cAMP/protein kinase A pathway as well as the protein kinase C pathway. KCNK6 is inactivated by heat and is characterized by a conductance lower than 5 pS. Taken together, these functional properties clearly differentiate KCNK6 from the other 2P domain K⁺ channels. The baseline activity of KCNK6 suggests that these channels may contribute to the setting of cellular resting membrane potential. Rapid inactivation of KCNK6 at physiological temperature converts the background K⁺ channel to an A-type K⁺ channel at the depolarizing potential. KCNK6 may contribute to the early repolarization of the action potential. Even at extreme depolarization potentials, the complete inactivation of KCNK6 means that a stable outward KCNK6 current may contribute to the later stages of action potential repolarization. KCNK6 should then be considered as a K⁺ channel that helps set the resting membrane potential and affects the early and late phases of action potential repolarization.

Fig.1 The structure of K2P channels family. KCNK6 belongs to K2P channels family.

Application of KCNK6 Membrane Protein in Literature

1. Bobak N., et al. Recombinant tandem of pore-domains in a Weakly Inward rectifying K⁺ channel 2 (TWIK2) forms active lysosomal channels. Sci Rep. 2017, 7(1):649. PubMed ID: 28381826
   
   

   These results indicated that TWIK2 produced a functional background K⁺ current in endolysosomes, whose expression affected the number and average size of lysosomes.

2. Pandit L.M., et al. TWIK-2 channel deficiency leads to pulmonary hypertension through a rho-kinase-mediated process. Hypertension. 2014, 64(6):1260-5. PubMed ID: 25245387
   
   

   The results suggested that downregulation of TWIK-2 in the pulmonary vasculature may be under underlying mechanism in the development of pulmonary hypertension.

3. Pathan A.R and Rusch N.J. Two-pore domain K⁺ channels: evidence for TWIK-2 in blood pressure regulation. Hypertension. 2011, 58(4):539-41. PubMed ID: 21876073
   
   

   This article revealed that the destruction of KCNK6 could produce vascular dysfunction and hypertension.

4. Sebastiani P., et al. Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study. Am J Hematol. 2010, 85(1):29-35. PubMed ID: 20029952
   
   

   The KCNK6 gene was associated with the severity of sickle cell anemia.

5. Mhatre A.N., et al. Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4. J Neurosci Res. 2004, 75(1):25-31. PubMed ID: 14689445
   
   

   DFNA4 was an autosomal dominant non-syndromic hereditary hearing loss. Identification and characterization of KCNK6 expression established this gene as a functional candidate for DFNA4.

KCNK6 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-KCNK6 antibody development services.

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