Linked Life Data

15140874

Source:http://linkedlifedata.com/resource/pubmed/id/15140874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-5-17
pubmed:abstractText
Stimulation of muscarinic acetylcholine receptors (mAChRs) can activate an inward rectifier K(+) current (I(KACh)), which is mediated by the M(2) subtype of mAChR in cardiac myocytes. Recently, a novel delayed rectifier-like K(+) current mediated by activation of the cardiac M(3) receptors (designated I(KM3)) was identified, which is distinct from I(KACh) and other known K(+) currents. While I(KACh) is known to be a G(i) protein-gated K(+) channel, the signal transduction mechanisms for I(KM3) activation remained unexplored. We studied I(KM3) with whole-cell patch clamp and macropatch clamp techniques. Whole cell I(KM3) activated by choline persisted with minimal rundown over 2 h in presence of internal GTP. When GTP was replaced by guanyl-5'-yl thiophosphate, I(KM3) demonstrated rapid and extensive rundown. While I(KACh) (induced by ACh) was markedly reduced in cells pretreated with pertussis toxin, I(KM3) was unaltered. Intracellular application of antibodies targeting alpha-subunit of G(i/o) protein suppressed I(KACh) without affecting I(KM3). Antibodies targeting the N and the C terminus, respectively, of G(q) protein alpha-subunit substantially depressed I(KM3) but failed to alter I(KACh). The antibody against beta-subunits of G proteins inhibited both I(KACh) and I(KM3). I(KM3) activated by choline in the cell-attached mode of macropatches persisted in the cell-free configuration. Application of purified G(q) protein alpha-subunit or betagamma-subunit of G proteins or guanosine 5'-O-(thiotriphosphate) to the internal solution activated I(KM3)-like currents in inside-out patches. Our findings revealed a novel aspect of receptor-channel signal transduction mechanisms, and I(KM3) represents the first G(q) protein-coupled K(+) channel. We propose that the G protein-coupled K(+) channel family could be divided into two subfamilies: G(i) protein-coupled K(+) channel subfamily and G(q) protein-coupled K(+) channel subfamily.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21774-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15140874-Animals, pubmed-meshheading:15140874-Cell-Free System, pubmed-meshheading:15140874-Cells, Cultured, pubmed-meshheading:15140874-Cloning, Molecular, pubmed-meshheading:15140874-DNA, Complementary, pubmed-meshheading:15140874-Dogs, pubmed-meshheading:15140874-Enzyme Activation, pubmed-meshheading:15140874-GTP-Binding Protein alpha Subunits, Gq-G11, pubmed-meshheading:15140874-Guanosine Triphosphate, pubmed-meshheading:15140874-Myocardium, pubmed-meshheading:15140874-Patch-Clamp Techniques, pubmed-meshheading:15140874-Pertussis Toxin, pubmed-meshheading:15140874-Potassium Channels, pubmed-meshheading:15140874-Protein Kinase C, pubmed-meshheading:15140874-Protein Structure, Tertiary, pubmed-meshheading:15140874-Receptor, Muscarinic M3, pubmed-meshheading:15140874-Receptors, G-Protein-Coupled, pubmed-meshheading:15140874-Signal Transduction, pubmed-meshheading:15140874-Time Factors
pubmed:year
2004
pubmed:articleTitle
The M3 receptor-mediated K(+) current (IKM3), a G(q) protein-coupled K(+) channel.
pubmed:affiliation
Research Center, Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't