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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1997-8-27
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pubmed:abstractText |
The pore-forming alpha 1 subunit of L-type calcium (Ca2+) channels is the molecular target of Ca2+ channel blockers such as phenylalkylamines (PAAs). Association and dissociation rates of (-)devapamil were compared for a highly PAA-sensitive L-type Ca2+ channel chimera (Lh) and various class A Ca2+ channel mutants. These mutants carry the high-affinity determinants of the PAA receptor site in a class A sequence environment. Apparent drug association and dissociation rate constants were significantly affected by the sequence environment (class A or L-type) of the PAA receptor site. Single point mutations affecting the high-affinity determinants in segments IVS6 of the PAA receptor site, introduced into a class A environment, reduced the apparent drug association rates. Mutation I1811M in transmembrane segment IVS6 (mutant AL25/-I) had the highest impact and decreased the apparent association rate for (-)devapamil by approximately 30-fold, suggesting that this pore-lining isoleucine in transmembrane segment IVS6 plays a key role in the formation of the PAA receptor site. In contrast, apparent drug dissociation rates of Ca2+ channels in the resting state were almost unaffected by point mutations of the PAA receptor site.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-1321525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-1330037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-1846962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-1849233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-2155469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-2414642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-2474130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-2539923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-271968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-2744488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-300786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-6086908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-6093100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-6289248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-6302512,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-7537420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-7574491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-7673189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-7682596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-7917287,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8210181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8524860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8562085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8574653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8584405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8662622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-8798706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9199780-9007846
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-3495
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
157-67
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9199780-Animals,
pubmed-meshheading:9199780-Binding Sites,
pubmed-meshheading:9199780-Calcium Channel Blockers,
pubmed-meshheading:9199780-Calcium Channels,
pubmed-meshheading:9199780-Calcium Channels, L-Type,
pubmed-meshheading:9199780-Macromolecular Substances,
pubmed-meshheading:9199780-Membrane Potentials,
pubmed-meshheading:9199780-Mutagenesis, Site-Directed,
pubmed-meshheading:9199780-Oocytes,
pubmed-meshheading:9199780-Recombinant Fusion Proteins,
pubmed-meshheading:9199780-Sequence Deletion,
pubmed-meshheading:9199780-Verapamil,
pubmed-meshheading:9199780-Xenopus
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pubmed:year |
1997
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pubmed:articleTitle |
Calcium channel block by (-)devapamil is affected by the sequence environment and composition of the phenylalkylamine receptor site.
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pubmed:affiliation |
Institut für Biochemische Pharmakologie, Innsbruck, Austria.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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