Source:http://linkedlifedata.com/resource/pubmed/id/12181125
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2002-8-15
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pubmed:abstractText |
DeltaKPQ, a three amino acid [lysine (K), proline (P), glutamine (Q)] deletion mutation of the human cardiac Na channel (hH1), which is one cause of long QT syndrome (LQT3), has impaired inactivation resulting in a late sodium current. To better understand inactivation in DeltaKPQ, we applied a site-3 toxin anthopleurin A, which has been shown to inhibit inactivation from the open state with little or no effect on inactivation from the closed state(s) in wild-type hH1. In contrast to the effect of site-3 toxins on wild-type hH1, inactivation from closed state(s) in toxin-modified DeltaKPQ demonstrated a large negative shift in the Na channel availability curve of nearly -14 mV. Recovery from inactivation showed that toxin-modified DeltaKPQ channels recovered slightly faster than those in control, whereas development of inactivation at potentials negative to -80 mV showed that inactivation developed much more rapidly in toxin-modified DeltaKPQ channels compared with control. An explanation for our results is that closed-state inactivation in toxin-modified DeltaKPQ is enhanced by the mutated inactivation lid being positioned "closer" to its receptor resulting in an increased rate of association between the inactivation lid and its receptor.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0363-6135
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H966-75
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12181125-Cardiotonic Agents,
pubmed-meshheading:12181125-Cell Line, Transformed,
pubmed-meshheading:12181125-Humans,
pubmed-meshheading:12181125-Ion Channel Gating,
pubmed-meshheading:12181125-Kidney,
pubmed-meshheading:12181125-Long QT Syndrome,
pubmed-meshheading:12181125-Membrane Potentials,
pubmed-meshheading:12181125-Mutation,
pubmed-meshheading:12181125-Patch-Clamp Techniques,
pubmed-meshheading:12181125-Peptides,
pubmed-meshheading:12181125-Sodium Channels
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pubmed:year |
2002
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pubmed:articleTitle |
Enhancement of closed-state inactivation in long QT syndrome sodium channel mutation DeltaKPQ.
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pubmed:affiliation |
The Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, Utah 84112, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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