Source:http://linkedlifedata.com/resource/pubmed/id/11742003
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2002-2-25
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| pubmed:abstractText |
We have investigated the functional consequences of three P/Q-type Ca(2+) channel alpha1A (Ca(v)2.1alpha(1)) subunit mutations associated with different forms of ataxia (episodic ataxia type 2 (EA-2), R1279Stop, AY1593/1594D; progressive ataxia (PA), G293R). Mutations were introduced into human alpha1A cDNA and heterologously expressed in Xenopus oocytes or tsA-201 cells (with alpha(2)delta and beta1a) for electrophysiological and biochemical analysis. G293R reduced current density in both expression systems without changing single channel conductance. R1279Stop and AY1593/1594D protein were expressed in tsA-201 cells but failed to yield inward barium currents (I(Ba)). However, AY1593/1594D mediated I(Ba) when expressed in oocytes. G293R and AY1593/1594D shifted the current-voltage relationship to more positive potentials and enhanced inactivation during depolarizing pulses (3 s) and pulse trains (100 ms, 1 Hz). Mutation AY1593/1594D also slowed recovery from inactivation. Single channel recordings revealed a change in fast channel gating for G293R evident as a decrease in the mean open time. Our data support the hypothesis that a pronounced loss of P/Q-type Ca(2+) channel function underlies the pathophysiology of EA-2 and PA. In contrast to other EA-2 mutations, AY1593/1594D and G293R form at least partially functional channels.
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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/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, N-Type,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/voltage-dependent calcium channel...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0021-9258
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| pubmed:author |
pubmed-author:EberhartAndreasA,
pubmed-author:GlossmannHartmutH,
pubmed-author:GrabnerManfredM,
pubmed-author:GroschnerKlausK,
pubmed-author:KoschakAlexandraA,
pubmed-author:KrausRichard LRL,
pubmed-author:PoteserMichaelM,
pubmed-author:SinneggerMartina JMJ,
pubmed-author:StriessnigJörgJ,
pubmed-author:WalterDorisD,
pubmed-author:WapplEdwinE
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| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
277
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6960-6
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11742003-Amino Acid Sequence,
pubmed-meshheading:11742003-Animals,
pubmed-meshheading:11742003-Ataxia,
pubmed-meshheading:11742003-Calcium Channels,
pubmed-meshheading:11742003-Calcium Channels, N-Type,
pubmed-meshheading:11742003-Cell Line,
pubmed-meshheading:11742003-Cloning, Molecular,
pubmed-meshheading:11742003-DNA, Complementary,
pubmed-meshheading:11742003-Electrophysiology,
pubmed-meshheading:11742003-Humans,
pubmed-meshheading:11742003-Kinetics,
pubmed-meshheading:11742003-Molecular Sequence Data,
pubmed-meshheading:11742003-Mutation,
pubmed-meshheading:11742003-Mutation, Missense,
pubmed-meshheading:11742003-Oocytes,
pubmed-meshheading:11742003-Sequence Homology, Amino Acid,
pubmed-meshheading:11742003-Time Factors,
pubmed-meshheading:11742003-Xenopus
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| pubmed:year |
2002
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| pubmed:articleTitle |
Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia.
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| pubmed:affiliation |
Institut für Biochemische Pharmakologie, Abteilung Pharmakologie und Toxikologie, Institut für Pharmazie, Universität Innsbruck, Peter-Mayrstrasse 1, A-6020 Innsbruck, Austria.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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