Linked Life Data

19752108

Source:http://linkedlifedata.com/resource/pubmed/id/19752108

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 21
pubmed:dateCreated
2009-11-2
pubmed:abstractText
Choline has been used widely as an agonist for the investigation of gain-of-function mutants of the nicotinic acetylcholine receptor. It is useful because it behaves like a partial agonist. The efficacy of choline is difficult to measure because choline blocks the channel at concentrations about four times lower than those that activate it. We have fitted activation mechanisms to single-channel activity elicited from HEK-expressed human recombinant muscle nicotinic receptors by choline and by tetramethylammonium (TMA). Channel block by the agonist was incorporated into the mechanisms that were fitted, and block was found not to be selective for the open state. The results also suggest that channel block is very fast and that the channel can shut almost as fast as normal when the blocker was bound. Single-channel data are compatible with a mechanism in which choline is actually a full agonist, its maximum response being limited only by channel block. However, they are also compatible with a mechanism incorporating a pre-opening conformation change ('flip') in which choline is a genuine partial agonist. The latter explanation is favoured by concentration jump experiments, and by the fact that only this mechanism fits the TMA data. We propose that choline, like TMA, is a partial agonist because it is very ineffective (approximately 600-fold less than acetylcholine) at eliciting the initial, pre-opening conformation change. Once flipping has occurred, all agonists, even choline, open the channel with similar efficiency.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1469-7793
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
587
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5045-72
pubmed:dateRevised
2010-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Agonist and blocking actions of choline and tetramethylammonium on human muscle acetylcholine receptors.
pubmed:affiliation
Department of Neuroscience, Physiology and Pharmacology, Medical Sciences Building, University College London, Gower St, London WC1E 6BT, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't