Source:http://linkedlifedata.com/resource/pubmed/id/15981012
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2005-11-28
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| pubmed:abstractText |
Voltage-gated sodium channels can be characterized by their sensitivity to inhibitors. Na(v)1.5 is sensitive to block by cadmium and extracellular QX-314, but relatively insensitive to tetrodotoxin and saxitoxin. Na(v)1.4 is tetrodotoxin- and saxitoxin-sensitive but resistant to cadmium and extracellular QX-314. Na(v)1.8 and Na(v)1.9 generate slowly inactivating (I(TTXr-Slow)) and persistent (I(TTXr-Per)) currents in sensory neurons that are tetrodotoxin-resistant. Tetrodotoxin sensitivity is largely determined by the identity of a single residue; tyrosine 401 in Na(v)1.4, cysteine 374 in Na(v)1.5 and serine 356 and 355 in Na(v)1.8 and Na(v)1.9. We asked whether Na(v)1.8 and Na(v)1.9 share other pharmacological properties as a result of this serine residue. I(TTXr-Slow) and I(TTXr-Per) were saxitoxin-resistant and resistant to internal QX-314. I(TTXr-Slow) was also resistant to external QX-314 and displayed a approximately fourfold higher sensitivity than I(TTXr-Per) to cadmium. The impact of the serine residue was investigated by replacing tyrosine 401 in Na(v)1.4 with serine (Y401S) or cysteine (Y401C). Both mutants were resistant to tetrodotoxin and saxitoxin. Whereas Na(v)1.4-Y401C displayed an increased sensitivity to cadmium and extracellular QX-314, the serine substitution did not alter the sensitivity of Na(v)1.4 to cadmium or QX-314. Our data indicates that while the serine residue determines the sensitivity of I(TTXr-Slow) and I(TTXr-Per) to tetrodotoxin and saxitoxin, it does not determine their insensitivity to QX-314 or their differential sensitivities to cadmium.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadmium,
http://linkedlifedata.com/resource/pubmed/chemical/Lidocaine,
http://linkedlifedata.com/resource/pubmed/chemical/QX-314,
http://linkedlifedata.com/resource/pubmed/chemical/Saxitoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0031-6768
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
451
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
454-63
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| pubmed:meshHeading |
pubmed-meshheading:15981012-Animals,
pubmed-meshheading:15981012-Cadmium,
pubmed-meshheading:15981012-Cell Line,
pubmed-meshheading:15981012-Extracellular Fluid,
pubmed-meshheading:15981012-Ganglia, Spinal,
pubmed-meshheading:15981012-Humans,
pubmed-meshheading:15981012-Intracellular Fluid,
pubmed-meshheading:15981012-Lidocaine,
pubmed-meshheading:15981012-Male,
pubmed-meshheading:15981012-Neurons, Afferent,
pubmed-meshheading:15981012-Patch-Clamp Techniques,
pubmed-meshheading:15981012-Rats,
pubmed-meshheading:15981012-Rats, Sprague-Dawley,
pubmed-meshheading:15981012-Saxitoxin,
pubmed-meshheading:15981012-Serine,
pubmed-meshheading:15981012-Sodium,
pubmed-meshheading:15981012-Sodium Channels,
pubmed-meshheading:15981012-Tetrodotoxin
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| pubmed:year |
2005
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| pubmed:articleTitle |
Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue.
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| pubmed:affiliation |
Klinik für Anästhesiologie, Friedrich-Alexander-Universität Erlangen-Nuremberg, Krankenhausstr. 12, 91054 Erlangen, Germany.
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| pubmed:publicationType |
Journal Article
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