PMID: 11901230Mar 20, 2002Paper

The batrachotoxin receptor on the voltage-gated sodium channel is guarded by the channel activation gate

Molecular Pharmacology
Hong-Ling LiDavid S Ragsdale

Abstract

Batrachotoxin (BTX), from South American frogs of the genus Phyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this study, we introduced a series of mutations at this site in the Na(v)1.3 sodium channel, expressed wild-type and mutant channels in Xenopus laevis oocytes, and examined their sensitivity to BTX using voltage clamp recording. We found that substitution of either alanine or isoleucine strongly reduced channel sensitivity to toxin, whereas cysteine, tyrosine, or tryptophan decreased toxin action only modestly. These data suggest an electrostatic ligand-receptor interaction at this site, possibly involving a charged tertiary amine on BTX. We then used a mutant channel (mutant F1710C) with intermediate toxin sensitivity to examine the properties of the toxin-receptor reaction in more detail. In contrast to wild-type channels, which bind BTX almost irreversibly, toxin dissociation from mutant channels was rapid, but only when the channels were open, not when they were closed. These data suggest the closed activation gate tr...Continue Reading

References

Mar 1, 1991·The Journal of General Physiology·J Tanguy, J Z Yeh
Jun 4, 1971·Science·E X AlbuquerqueB Witkop
Jun 1, 1973·The Journal of General Physiology·A M Woodhull
Jul 1, 1973·The Journal of General Physiology·G R Strichartz
Dec 1, 1981·Cellular and Molecular Neurobiology·G B Brown, J W Daly
Oct 20, 1981·Biochimica Et Biophysica Acta·B I KhodorovR Stämpfli
Nov 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·F N Quandt, T Narahashi
Jun 1, 1994·Pflügers Archiv : European journal of physiology·G K Wang, S Y Wang
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Y Wang, G K Wang
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·N J LinfordW A Catterall
Nov 22, 2000·Biochimie·S Cestèle, W A Catterall

❮ Previous
Next ❯

Citations

Mar 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Chris R FeldmanMichael E Pfrender
Feb 10, 2011·The Journal of Biological Chemistry·Yuzhe DuKe Dong
Mar 11, 2003·The Journal of Physiology·Ging Kuo Wang, Sho-Ya Wang
Nov 6, 2004·FEBS Letters·Frank BosmansJan Tytgat
Jan 25, 2006·British Journal of Pharmacology·Mariana Oana Popa, Holger Lerche
Jul 30, 2003·Biophysical Journal·Sho-Ya WangGing Kuo Wang
May 27, 2016·ACS Chemical Neuroscience·Luisa Ribeiro-SilvaManoel Arcisio-Miranda
Sep 27, 2005·Physiological Reviews·Werner Ulbricht
Sep 5, 2012·ChemMedChem·Antonio NardiAchim Kless
Dec 28, 2018·The Journal of General Physiology·Rocio K Finol-UrdanetaRobert J French
Jan 29, 2021·Journal of Theoretical Biology·Marcelo OteroJavier A Ramírez
Feb 11, 2020·Journal of the American Chemical Society·Yinliang GuoTuoping Luo
Oct 21, 2016·ACS Chemical Neuroscience·Tatsuya TomaJ Du Bois

❮ 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.