High-affinity binding sites for [3H]saxitoxin are associated with voltage-dependent sodium channels in portal vein smooth muscle.
Abstract: Saturable, high-affinity binding sites for [3H]saxitoxin were identified in equine portal vein smooth muscle membranes. These sites had a dissociation constant of 0.29 nM and a maximal binding capacity of 115 fmol.mg-1 of protein. A similar dissociation constant was obtained with cells prepared from rat portal vein. Specific binding of [3H]saxitoxin was completely displaced by unlabelled saxitoxin and tetrodotoxin, with inhibition constants of 0.42 and 2.10 nM, respectively. Tetrodotoxin blocked the fast Na+ current in single cells of rat portal vein in a concentration-dependent manner, with an IC50 of 3.15 nM. These results suggest that the high-affinity binding sites for tetrodotoxin and saxitoxin may be associated with voltage-dependent Na+ channels in vascular myocytes.
Publication Date: 1990-08-10 PubMed ID: 1964130DOI: 10.1016/0014-2999(90)90624-fGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper discusses the discovery of high-affinity binding sites for a toxin called saxitoxin in the smooth muscle membranes of the portal vein. These binding sites are associated with voltage-dependent sodium channels, which play a crucial role in cell function.
Discovery of Saxitoxin Binding Sites
- The scientists identified high-affinity binding sites for saxitoxin in the smooth muscle membranes of the equine portal vein.
- These binding sites had a specific dissociation constant—a measure of how effectively a compound like saxitoxin binds to a receptor or site—and a maximal binding capacity, indicating the largest amount of saxitoxin these sites could hold.
Saxitoxin Binding Properties
- They also found that cells from the rat portal vein had a similar dissociation constant, showing that this property is not unique to equine cells.
- When unlabelled saxitoxin and a similarly functioning toxin called tetrodotoxin were introduced, they displaced the labelled saxitoxin from the binding sites.
- This indicates that saxitoxin and tetrodotoxin compete for the same sites, and that these toxins impede each other’s binding.
Influence of Tetrodotoxin
- The scientists found that tetrodotoxin inhibited the fast sodium current—a crucial flow of ions that affects cell function— in the rat portal vein cells in a concentration-dependent manner.
- This suggests that higher concentrations of tetrodotoxin result in greater inhibition of this current. To measure this, the researchers used a half-maximal inhibitory concentration (IC50)—the amount of a substance needed to inhibit a biological process by half.
Connection to Sodium Channels
- From these results, the scientists propose that the high-affinity binding sites for tetrodotoxin and saxitoxin may be associated with voltage-dependent sodium channels in vascular myocytes, or muscle cells.
- If further supported, this finding could have significant implications for understanding the function of these cells and their response to toxins.
Cite This Article
APA
Mironneau J, Martin C, Arnaudeau S, Jmari K, Rakotoarisoa L, Sayet I, Mironneau C.
(1990).
High-affinity binding sites for [3H]saxitoxin are associated with voltage-dependent sodium channels in portal vein smooth muscle.
Eur J Pharmacol, 184(2-3), 315-319.
https://doi.org/10.1016/0014-2999(90)90624-f Publication
Researcher Affiliations
- Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, INSERM JF 88-13, Bordeaux, France.
MeSH Terms
- Amphibian Proteins
- Animals
- Carrier Proteins / analysis
- Horses
- In Vitro Techniques
- Membrane Potentials / drug effects
- Membranes / metabolism
- Muscle, Smooth, Vascular / chemistry
- Portal Vein / chemistry
- Rats
- Saxitoxin / metabolism
- Sodium Channels / chemistry
- Tetrodotoxin / pharmacology
- Tritium
Citations
This article has been cited 8 times.- Ho WS, Davis AJ, Chadha PS, Greenwood IA. Effective contractile response to voltage-gated Na+ channels revealed by a channel activator. Am J Physiol Cell Physiol 2013 Apr 15;304(8):C739-47.
- Bocquet A, Sablayrolles S, Vacher B, Le Grand B. F 15845, a new blocker of the persistent sodium current prevents consequences of hypoxia in rat femoral artery. Br J Pharmacol 2010 Sep;161(2):405-15.
- Zhu HL, Aishima M, Morinaga H, Wassall RD, Shibata A, Iwasa K, Nomura M, Nagao M, Sueishi K, Cunnane TC, Teramoto N. Molecular and biophysical properties of voltage-gated Na+ channels in murine vas deferens. Biophys J 2008 Apr 15;94(8):3340-51.
- Saleh S, Yeung SY, Prestwich S, Pucovsky V, Greenwood I. Electrophysiological and molecular identification of voltage-gated sodium channels in murine vascular myocytes. J Physiol 2005 Oct 1;568(Pt 1):155-69.
- Hollywood MA, Cotton KD, Thornbury KD, McHale NG. Tetrodotoxin-sensitive sodium current in sheep lymphatic smooth muscle. J Physiol 1997 Aug 15;503 ( Pt 1)(Pt 1):13-20.
- Xiong Z, Sperelakis N, Noffsinger A, Fenoglio-Preiser C. Fast Na+ current in circular smooth muscle cells of the large intestine. Pflugers Arch 1993 Jun;423(5-6):485-91.
- Muraki K, Imaizumi Y, Watanabe M. Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea-pig. J Physiol 1991 Oct;442:351-75.
- Mironneau J, Yamamoto T, Sayet I, Arnaudeau S, Rakotoarisoa L, Mironneau C. Effect of dihydropyridines on calcium channels in isolated smooth muscle cells from rat vena cava. Br J Pharmacol 1992 Feb;105(2):321-8.
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