| Recent advances in the study of mechanism of action of marine neurotoxins. | |
| | |
MedLine Citation:
|
PMID: 7854588 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A variety of marine neurotoxins exert potent and specific actions on neuronal sodium channels. Tetrodotoxin and saxitoxin block the sodium channel selectively without any effect on other types of voltage-activated and transmitter-activated ion channels. They bind to a site near the external orifice of the sodium channel on a one-to-one stoichiometric basis. The block is influenced by the membrane potential in a complex manner, and binding and penetration of calcium ions to the sodium channel appear to be responsible for the voltage-dependent block. Owing to the potent and specific sodium channel blocking action, tetrodotoxin and saxitoxin have been used extensively in various studies of ion channels. The dorsal root ganglion neurons of the rat are endowed with tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. The latter is also resistant to saxitoxin. These two types of sodium channels exhibit different physiological and pharmacological profiles. Tetrodotoxin-resistant sodium channels are slower in time course and open and inactivate at less negative membrane potentials than tetrodotoxin-sensitive sodium channels. Lidocaine blocks tetrodotoxin-sensitive sodium channels more potently than tetrodotoxin-resistant sodium channels. However, Pb2+ and Cd2+ block tetrodotoxin-resistant channels more strongly. The pyrethroid insecticide allethrin modifies tetrodotoxin-resistant sodium channels while affecting tetrodotoxin-sensitive sodium channels to a much lesser extent. The differences in pharmacological and toxicological profiles between the two types of sodium channels are deemed critically important in understanding the mechanisms of action of various chemicals in animals. |
| | |
Authors:
|
T Narahashi; M L Roy; K S Ginsburg |
Related Documents
:
|
18221218 - Blockers of voltage-gated sodium channels for the treatment of central nervous system d... 15129178 - Expression of tetrodotoxin-sensitive and resistant sodium channels by rat melanotrophs. 16038878 - Neuronal sodium channels in ventricular heart cells are localized near t-tubules openings. 16374428 - Biphasic changes of epithelial sodium channel abundance and trafficking in common bile ... 8989398 - Arachidonic-acid-activated membrane conductances in dissociated cardiac parasympathetic... 11156298 - Determining k+ channel activation curves from k+ channel currents. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
|
Title: Neurotoxicology Volume: 15 ISSN: 0161-813X ISO Abbreviation: Neurotoxicology Publication Date: 1994 |
Date Detail:
|
Created Date: 1995-03-16 Completed Date: 1995-03-16 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 7905589 Medline TA: Neurotoxicology Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 545-54 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Humans Neurotoxins / pharmacology* Patch-Clamp Techniques Saxitoxin / pharmacology* Sodium Channels / drug effects* Tetrodotoxin / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
|
NS14143/NS/NINDS NIH HHS; NS14144/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Neurotoxins; 0/Sodium Channels; 35523-89-8/Saxitoxin; 4368-28-9/Tetrodotoxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Excitotoxins in foods.
Next Document: Nutrition and alcohol neurotoxicity.