Identification of sites responsible for the potentiating effect of niflumic acid on ClC-Ka kidney chloride channels.

British Journal of Pharmacology
Giovanni ZifarelliMichael Pusch

Abstract

ClC-K kidney Cl(-) channels are important for renal and inner ear transepithelial Cl(-) transport, and are potentially interesting pharmacological targets. They are modulated by niflumic acid (NFA), a non-steroidal anti-inflammatory drug, in a biphasic way: NFA activates ClC-Ka at low concentrations, but blocks the channel above approximately 1 mM. We attempted to identify the amino acids involved in the activation of ClC-Ka by NFA. We used site-directed mutagenesis and two-electrode voltage clamp analysis of wild-type and mutant channels expressed in Xenopus oocytes. Guided by the crystal structure of a bacterial CLC homolog, we screened 97 ClC-Ka mutations for alterations of NFA effects. Mutations of five residues significantly reduced the potentiating effect of NFA. Two of these (G167A and F213A) drastically altered general gating properties and are unlikely to be involved in NFA binding. The three remaining mutants (L155A, G345S and A349E) severely impaired or abolished NFA potentiation. The three key residues identified (L155, G345, A349) are localized in two different protein regions that, based on the crystal structure of bacterial CLC homologs, are expected to be exposed to the extracellular side of the channel, relativ...Continue Reading

References

Oct 1, 1980·The Journal of Physiology·F J Sigworth
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·S KieferleT J Jentsch
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·C LorenzT J Jentsch
Jan 3, 2001·American Journal of Physiology. Renal Physiology·N AkizukiF Marumo
Jul 12, 2002·Pflügers Archiv : European journal of physiology·Siegfried WaldeggerHannsjörg W Seyberth
Oct 3, 2002·European Journal of Pharmacology·Anna P MalykhinaHamid I Akbarali
Mar 22, 2003·Science·Raimund DutzlerRoderick MacKinnon
Aug 13, 2003·The Journal of General Physiology·Alessio Accardi, Michael Pusch
Mar 27, 2004·The New England Journal of Medicine·Karl P SchlingmannSiegfried Waldegger
May 29, 2004·EMBO Reports·Alessandra PicolloMichael Pusch
Jun 2, 2004·EMBO Reports·Peying Fong
Jan 27, 2005·Circulation Journal : Official Journal of the Japanese Circulation Society·Yoshihiro KokuboHitonobu Tomoike
Feb 16, 2005·Annual Review of Physiology·Shinichi Uchida, Sei Sasaki
Apr 15, 2005·Journal of the American Society of Nephrology : JASN·Thomas J Jentsch
Oct 26, 2005·Molecular Pharmacology·Antonella LiantonioDiana Conte Camerino
Jul 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ute SchollChristoph Fahlke
Dec 8, 2006·Trends in Pharmacological Sciences·Iain A Greenwood, Normand Leblanc
Jun 15, 2007·Neurochemistry International·Leanne CoyneRobert F Halliwell
Jul 31, 2007·The Journal of Membrane Biology·Alessandra PicolloMichael Pusch
Aug 31, 2007·Reviews of Physiology, Biochemistry and Pharmacology·G Zifarelli, M Pusch
Jan 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Antonella LiantonioDiana Conte Camerino
Jan 26, 2008·Molecular Pharmacology·David FernandezMichael C Sanguinetti
May 2, 2008·British Journal of Pharmacology·S P H AlexanderJ A Peters
Apr 16, 2008·The Journal of General Physiology·Gregory J KaczorowskiMaria L Garcia
Jul 23, 2008·ACS Chemical Biology·Kimberly MatulefMerritt Maduke

❮ Previous
Next ❯

Citations

Sep 2, 2010·The Journal of General Physiology·Antonella GradognaMichael Pusch
Jan 30, 2013·Pharmacology & Therapeutics·Romain GuinamardChristopher Del Negro
May 28, 2014·Biochimica Et Biophysica Acta·Paola ImbriciDiana Conte Camerino
Sep 5, 2012·The Journal of Pharmacy and Pharmacology·Asfree GwanyanyaKanigula Mubagwa
Mar 13, 2015·The Journal of Physiology·Alejandro Barrallo-GimenoRaúl Estévez
Jul 5, 2013·Biophysical Journal·Antonella Gradogna, Michael Pusch
Jul 30, 2014·Biochimica Et Biophysica Acta·Antonella GradognaMichael Pusch
Jun 25, 2013·Biochimica Et Biophysica Acta·Sébastien L'HosteStéphane Lourdel
May 31, 2018·Physiological Reviews·Thomas J Jentsch, Michael Pusch
Jan 13, 2019·Journal of the American Society of Nephrology : JASN·Laura LagostenaAlessandra Picollo
Jul 19, 2013·American Journal of Physiology. Renal Physiology·Jerod S DentonMerritt Maduke
Jun 1, 2017·Frontiers in Molecular Neuroscience·Galyna MaleevaPiotr Bregestovski
Dec 20, 2018·American Journal of Physiology. Cell Physiology·Viktor YarotskyyGeorgi V Petkov

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Antonella LiantonioDiana Conte Camerino
Journal of the American Society of Nephrology : JASN
Martin FischerChristoph Fahlke
© 2021 Meta ULC. All rights reserved