Linked Life Data

12867984

Source:http://linkedlifedata.com/resource/pubmed/id/12867984

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6946
pubmed:dateCreated
2003-7-17
pubmed:abstractText
5-hydroxytryptamine type 3 (5-HT3) receptors are cation-selective transmitter-gated ion channels of the Cys-loop superfamily. The single-channel conductance of human recombinant 5-HT3 receptors assembled as homomers of 5-HT3A subunits, or heteromers of 5-HT3A and 5-HT3B subunits, are markedly different, being 0.4 pS (refs 6, 9) and 16 pS (ref. 7), respectively. Paradoxically, the channel-lining M2 domain of the 5-HT3A subunit would be predicted to promote cation conduction, whereas that of the 5-HT3B subunit would not. Here we describe a determinant of single-channel conductance that can explain these observations. By constructing chimaeric 5-HT3A and 5-HT3B subunits we identified a region (the 'HA-stretch') within the large cytoplasmic loop of the receptor that markedly influences channel conductance. Replacement of three arginine residues unique to the HA-stretch of the 5-HT3A subunit by their 5-HT3B subunit counterparts increased single-channel conductance 28-fold. Significantly, ultrastructural studies of the Torpedo nicotinic acetylcholine receptor indicate that the key residues might frame narrow openings that contribute to the permeation pathway. Our findings solve the conundrum of the anomalously low conductance of homomeric 5-HT3A receptors and indicate an important function for the HA-stretch in Cys-loop transmitter-gated ion channels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
424
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
321-4
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12867984-Amino Acid Sequence, pubmed-meshheading:12867984-Arginine, pubmed-meshheading:12867984-Cations, pubmed-meshheading:12867984-Conserved Sequence, pubmed-meshheading:12867984-Cysteine, pubmed-meshheading:12867984-Cytoplasm, pubmed-meshheading:12867984-Electric Conductivity, pubmed-meshheading:12867984-Electrophysiology, pubmed-meshheading:12867984-Fluorescent Antibody Technique, pubmed-meshheading:12867984-Humans, pubmed-meshheading:12867984-Ion Channels, pubmed-meshheading:12867984-Molecular Sequence Data, pubmed-meshheading:12867984-Protein Structure, Tertiary, pubmed-meshheading:12867984-Protein Subunits, pubmed-meshheading:12867984-Receptors, Serotonin, pubmed-meshheading:12867984-Receptors, Serotonin, 5-HT3, pubmed-meshheading:12867984-Recombinant Fusion Proteins
pubmed:year
2003
pubmed:articleTitle
A cytoplasmic region determines single-channel conductance in 5-HT3 receptors.
pubmed:affiliation
Neurosciences Institute, Department of Pharmacology and Neuroscience, Ninewells Hospital and Medical School, The University of Dundee, Dundee DD1 9SY, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't