CLCNKA Membrane Protein Introduction

Introduction of CLCNKA

CLCNKA, also known as chloride channel Ka, is a protein that is encoded by the CLCNKA gene in humans. Different isoforms encoded by multiple transcript variants have been found for this gene, including CLCNKA and CLCNKB. Both of them are widely existing in the kidney. The CLCNKA gene is subject to variation due to single-nucleotide polymorphisms (SNPs). Under this principle, a single base (A, T, C, or G) is rarely replaced by others. SNPs in the coding regions of CLCKNA may have consequent changes in the amino acid sequence of the ClC-Ka chloride channel, which may lead to changed function and physiological alterations.

Function of CLCNKA Membrane Protein

Chloride channel protein ClC-Ka (CLCNKA) is an important member of the CLC family of voltage-gated chloride channels. The encoded protein tends to have 10 transmembrane domains. When forming the functional channel, it requires help from barttin (a beta subunit). This protein is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. Besides, CLCNKA involves many molecular and biological processes. It can regulate identical protein binding, metal ion binding, and voltage-gated chloride channel activity. What’s more, it also has effects on cell volume, membrane potential stabilization, signal transduction, and transepithelial transport. It may also play an important role in urinary concentrating mechanisms. This protein can be activated by extracellular calcium and inhibited by extracellular protons. Activation of the CNCLKA can participate in sensation processes such as pain, warmth, cold, taste pressure and vision through stimuli-sensing channels.

Fig.1 ClC-K channels are expressed in kidney and inner ear. (A) At the nephrons, luminal NKCC2 transporters build up Na⁺, K⁺ and Cl^- into the cells. K⁺ flows back to the lumen through ROMK1 channels; Na⁺ and Cl^- are reabsorbed to the bloodstream separately through Na+/K+ ATPase and ClC-Kb channels, respectively. (B) In the Stria Vascularis, Na⁺, K⁺ and Cl^- are transported into the cells by basolateral NKCC1 transporters. Na⁺ and Cl^- are recycled back to the interstitium by Na⁺/K⁺ ATPase and both ClC-Ks isomers, respectively. K⁺ flows through KCNQ1/KCNE1 channels and accumulates into the endolymph, a condition required for sensory transduction in inner hair cells. (Poroca, 2017)

Application of CLCNKA Membrane Protein in Literature

1. Barlassina C., et al. Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension. Hum. Mol. Genet. 2007, 16(13):1630-8. PubMed ID: 17510212
   
   

   This article finds that chloride channels CLC-Ka (gene CLCNKA) and CLC-Kb (gene CLCNKB) and their subunit Barttin (gene BSND) have important effects on the control of Na(+) and water homeostasis in the kidney. And the candidacy of CLCNKA might be a new susceptibility gene for salt-sensitivity.

2. Cappola T.P., et al. Loss-of-function DNA sequence variant in the CLCNKA chloride channel implicates the cardio-renal axis in interindividual heart failure risk variation. Proc. Natl. Acad. Sci. 2011, 108 (6): 2456–61. PubMed ID: 21248228
   
   

   This article shows that the SNP marks the position of a functional variant in another gene. Those results identify a common, functionally significant genetic risk factor for Caucasian heart failure. The variant CLCNKA risk allele, telegraphed uncovers a previously overlooked genetic mechanism which affects the cardio-renal axis by linked variants in the adjacent HSPB7 gene.

3. Imbrici P., et al. Pharmacovigilance database search discloses ClC-K channels as a novel target of the AT1receptor blockers valsartan and olmesartan. Br J Pharmacol. 2017, 174(13):1972-1983. PubMed ID: 28334417
   
   

   The results in this article show that valsartan and olmesartan are able to block the expression of ClC-Ka channels and the molecular requirements of effective inhibition of these channels have been identified. Moreover, additional mechanisms of action for these sartans further to their primary AT₁ receptor antagonism and propose these compounds as leads for designing new potent ClC-K ligands.

4. Chen X., et al. Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China. Clin Exp Hypertens. 2015, 37(7):519-25. PubMed ID: 25919862
   
   

   This article shows that samples with the tag SNPs of CLCNKA_B are marginally associated with the decreased risk of EH in GMDR. The results indicate that, although the combination of tag SNPs of CLCNKA_B is not enough to significantly increase the EH susceptibility, the further combination of CLCNKA tag SNP, salt, marine products, meat and edible oil consumption is associated with elevated risk.

5. Imbrici P., et al. Targeting kidney CLC-K channels: pharmacological profile in a human cell line versus Xenopus oocytes. Biochim Biophys Acta. 2014, 1838(10):2484-91. PubMed ID: 24863058
   
   

   This article finds that the niflumic acid block does not have an effect on the accessory subunit barttin on CLC-K1 channels. In addition, the sensitivity of CLC-Ks to external Ca(2+) is reduced. In conclusion, the authors propose that mammalian cell lines are a suitable expression system for the pharmacological profiling of CLC-Ks.

CLCNKA Preparation Options

Membrane protein studies have got great progress over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services in reconstitution forms as well as multiple active formats for worldwide customers. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CNCLKA 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. It’s our pleasure to boost 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. Poroca D R, et al. (2017). ClC channels and transporters: structure, physiological functions, and implications in human chloride channelopathies. Frontiers in pharmacology. 8, 151.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.