Linked Life Data

10956662

Source:http://linkedlifedata.com/resource/pubmed/id/10956662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2000-12-29
pubmed:abstractText
Mechanisms and residues responsible for slow activation and Ba(2+) block of the cardiac muscarinic K(+) channel, Kir3.1/Kir3.4, were investigated using site-directed mutagenesis. Mutagenesis of negatively charged residues located throughout the pore of the channel (in H5, M2, and proximal C terminus) reduced or abolished slow activation. The strongest effects resulted from mutagenesis of residues in H5 close to the selectivity filter; mutagenesis of residues in M2 and proximal C terminus equivalent to those identified as important determinants of the activation kinetics of Kir2.1 was less effective. In giant patches, slow activation was present in cell-attached patches, lost on excision of the patch, and restored on perfusion with polyamine. Mutagenesis of residues in H5 and M2 close to the selectivity filter also decreased Ba(2+) block of the channel. A critical residue for Ba(2+) block was identified in Kir3.4. Mutagenesis of the equivalent residue in Kir3.1 failed to have as pronounced an effect on Ba(2+) block, suggesting an asymmetry of the channel pore. It is concluded that slow activation is principally the result of unbinding of polyamines from negatively charged residues close to the selectivity filter of the channel and not an intrinsic gating mechanism. Ba(2+) block involves an interaction with the same residues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35831-9
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:10956662-Animals, pubmed-meshheading:10956662-Barium, pubmed-meshheading:10956662-DNA, Complementary, pubmed-meshheading:10956662-Dose-Response Relationship, Drug, pubmed-meshheading:10956662-G Protein-Coupled Inwardly-Rectifying Potassium Channels, pubmed-meshheading:10956662-Kinetics, pubmed-meshheading:10956662-Magnesium, pubmed-meshheading:10956662-Microinjections, pubmed-meshheading:10956662-Mutation, pubmed-meshheading:10956662-Myocardium, pubmed-meshheading:10956662-Oocytes, pubmed-meshheading:10956662-Patch-Clamp Techniques, pubmed-meshheading:10956662-Polyamines, pubmed-meshheading:10956662-Potassium Channel Blockers, pubmed-meshheading:10956662-Potassium Channels, pubmed-meshheading:10956662-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:10956662-Xenopus
pubmed:year
2000
pubmed:articleTitle
Residues and mechanisms for slow activation and Ba2+ block of the cardiac muscarinic K+ channel, Kir3.1/Kir3.4.
pubmed:affiliation
School of Biomedical Sciences and Biochemistry & Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom. m.k.lancaster@leeds.ac.uk
pubmed:publicationType
Journal Article