rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2000-9-18
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pubmed:abstractText |
The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage-dependent block of IHERG. Significant inhibition was seen at concentrations as low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV; at more positive potentials, inhibition decreased in association with time-dependent unblocking of channels. An inactivation-attenuated mutant of HERG (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A differed from that of HERG in that extensive unblocking was no longer seen at positive potentials and the voltage dependence of step current block was greatly attenuated. A mathematical model was applied to analyse quantitatively the inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage-dependent affinity of Ba2+ for the open and closed states, along with absence of binding to the inactivated state, and accounted well for Ba2+ effects on both wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a characteristic state-dependent fashion, with strong unblocking at positive potentials related to the presence of an intact C-type inactivation mechanism.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10896755-10086971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10896755-10096894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10896755-10219239,
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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/Barium,
http://linkedlifedata.com/resource/pubmed/chemical/Cation Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ERG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ERG1 potassium channel,
http://linkedlifedata.com/resource/pubmed/chemical/Ether-A-Go-Go Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/KCNH6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-3751
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
526 Pt 2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
265-78
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10896755-Amino Acid Substitution,
pubmed-meshheading:10896755-Animals,
pubmed-meshheading:10896755-Barium,
pubmed-meshheading:10896755-Cation Transport Proteins,
pubmed-meshheading:10896755-DNA-Binding Proteins,
pubmed-meshheading:10896755-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:10896755-Female,
pubmed-meshheading:10896755-Humans,
pubmed-meshheading:10896755-Kinetics,
pubmed-meshheading:10896755-Long QT Syndrome,
pubmed-meshheading:10896755-Membrane Potentials,
pubmed-meshheading:10896755-Models, Theoretical,
pubmed-meshheading:10896755-Mutagenesis, Site-Directed,
pubmed-meshheading:10896755-Oocytes,
pubmed-meshheading:10896755-Patch-Clamp Techniques,
pubmed-meshheading:10896755-Potassium Channels,
pubmed-meshheading:10896755-Potassium Channels, Voltage-Gated,
pubmed-meshheading:10896755-Trans-Activators,
pubmed-meshheading:10896755-Xenopus laevis
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pubmed:year |
2000
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