Linked Life Data

14694085

Source:http://linkedlifedata.com/resource/pubmed/id/14694085

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-1
pubmed:abstractText
ATP-sensitive potassium (K(ATP)) channels are crucial to pancreatic endocrine function and their activation by acyl coenzyme A esters (acyl CoAs) may disrupt hormone secretion, contributing to the pathophysiology of type 2 diabetes. The molecular mechanism of this activation is potentially important in our further understanding of this disease. We use excised patch-clamp techniques to assess the effects of N- and C-terminal Kir6.2 mutations on the activation of recombinant K(ATP) channels by palmitoyl CoA. We demonstrate that several residues previously shown to be involved in channel activation by the structurally related lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) also play a role in activation by acyl CoAs, including R54, R176, R192, and R301. Mutation of these residues caused decreased open probability in the absence of ATP and slower and greater relative activation by both PIP(2) and acyl CoAs. By contrast, K185Q, which probably alters ATP binding, had no effect on either PIP(2) or palmitoyl CoA activation. These findings suggest that activation by the two classes of lipids involves multiple common residues. We use the crystal structure of a related channel, KirBac1.1, as a template to locate the residues of interest in this study within a putative three-dimensional model of Kir6.2. We propose a model in which these residues mediate both direct electrostatic interactions and allosteric modulations of open state stability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
679-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Activation of adenosine triphosphate-sensitive potassium channels by acyl coenzyme A esters involves multiple phosphatidylinositol 4,5-bisphosphate-interacting residues.
pubmed:affiliation
Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. jmanningfox@pmcol.ualberta.ca
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't