Linked Life Data

9489744

Source:http://linkedlifedata.com/resource/pubmed/id/9489744

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-3-12
pubmed:abstractText
Voltage-gated sodium channels serve as a target for many neurotoxins that bind to several distinct, allosterically interacting receptor sites. We examined the effect of membrane potentials (incited by increasing external K+ concentrations) on the binding modulation by veratridine, brevetoxin, and tetrodotoxin of the scorpion alpha-toxin AaH II to receptor site 3 on sodium channels of rat brain synaptosomes. Depolarization is shown to differentially modulate neurotoxin effects on AaH II binding: Veratridine increase is potentiated, brevetoxin's inhibitory effect is reduced, and tetrodotoxin enhancement is evident mainly at resting membrane potential (5 mM K+). Both tetrodotoxin and veratridine apparently reverse the inhibition of AaH II binding by brevetoxin at resting membrane potential, but only veratridine is able to partially restore AaH II binding at 0 mV (135 mM K+). Thus, the allosteric interactions are grouped into two categories, depending on the membrane potential. Under depolarized conditions, the cooperative effects among veratridine and brevetoxin on AaH II binding fit the previously described two-state conformational model. At resting membrane potential, additional interactions are revealed, which may be explained by assuming that toxin binding induces conformational changes on the channel structure, in addition to being state-dependent. Our results provide a new insight into neurotoxin action and the complex dynamic changes underlying allosteric coupling of neurotoxin receptor sites, which may be related to channel gating.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1217-26
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Depolarization differentially affects allosteric modulation by neurotoxins of scorpion alpha-toxin binding on voltage-gated sodium channels.
pubmed:affiliation
Laboratoire de Biochimie, CNRS URA 1455, Faculté de Médicine Nord, Jean Roche Institut, Marseille, France.
pubmed:publicationType
Journal Article