Linked Life Data

19063861

Source:http://linkedlifedata.com/resource/pubmed/id/19063861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-9
pubmed:abstractText
The highly conserved alphaLys145 has been suggested to play an important role in the early steps of activation of the nicotinic acetylcholine receptor (nAChR) by acetylcholine. Both macroscopic and single channel currents were recorded in the slowly desensitizing mutants L248T- and K145A-L248T-alpha7 receptors expressed in Xenopus oocytes. On ACh-evoked currents, substitution of Lys145 by alanine showed the same effects that in wild type receptors: moderately decreased gating function and a more-than-expected loss of ACh potency, thus validating the experimental model. Single channel analysis quantitatively agreed with macroscopic data and revealed that impaired gating function in the double mutant alpha7K145A/L248T is the consequence of a slower opening rate, beta. Several nicotinic agonists were also studied, showing important features. Particularly, dimethylphenylpiperazinium (DMPP), acting as an antagonist in alpha7K145A, became a full agonist in alpha7K145A/L248T. Single channel analysis of DMPP-evoked currents showed effects of Lys145 removal similar to those observed with ACh. Data suggest that alpha7Lys145 facilitates the early steps of channel activation. Moreover, the slowly desensitizing mutant alpha7L248T could be an interesting tool for the study of channel activation in alpha7 receptors. Nevertheless, its extensively altered pharmacology precludes the simple extrapolation of pharmacological data obtained in singly mutated alpha7 receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1788
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
410-6
pubmed:dateRevised
2010-6-4
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Binding-gating coupling in a nondesensitizing alpha7 nicotinic receptor A single channel pharmacological study.
pubmed:affiliation
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, 03550-Alicante, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't