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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1989-7-31
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pubmed:abstractText |
The functional mechanisms of noncompetitive blockade of the nicotinic acetylcholine receptor from the BC3H-1 cell line were examined using single-channel currents recorded from cell-attached patches. Channel open times were distributed as sums of two exponentials and the closed times as sums of at least four exponentials. The single-channel currents of the receptor were analyzed in terms of activation schemes in which the receptor exists in two open states and a number of closed or blocked states. The existence of two distinct open states for the acetylcholine receptor allows for predictions to be made that will distinguish between different mechanisms of blockade. Notably, predictions could be made based on the model for the sequential block of open channels, that would allow us to discriminate such a mechanism, even for ligands that appear to dissociate so slowly that sequential openings of the same channel do not appear as distinct bursts. Four noncompetitive blockers of the acetylcholine receptor were studied: tetracaine, phencyclidine, and the (+) and (-) isomers of N-allylnormetazocine (SKF-10047). All four of these ligands decreased the duration of single-channel currents without increasing the number of fast closures per burst. The data suggest that the ligands block the channel in at least two distinct ways, one of which involves a specific interaction with open channels and the other is most consistent with the blockade of channels that may be either open or closed. In addition, the duration of the open state may be allosterically lengthened by the interaction of certain blockers with another class of sites.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-174144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2416894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2419552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2420977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2422653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2427693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2432254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2443668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2447968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-2860110,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-3670280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-3951431,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-400609,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6090885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6130531,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6248795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6270629,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6882740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6943590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-6953408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-7085658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2472461-806679
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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 |
May
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pubmed:issn |
0022-1295
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
785-811
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
1989
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pubmed:articleTitle |
Mechanisms of noncompetitive inhibition of acetylcholine-induced single-channel currents.
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pubmed:affiliation |
Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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