Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-11-21
pubmed:abstractText
Mitochondria in a variety of cell types respond to physiological Ca(2+) oscillations in the cytosol dynamically with Ca(2+) uptakes. In heart cells, mitochondrial Ca(2+) uptakes occur by a ruthenium red-sensitive Ca(2+) uniporter (CaUP), a rapid mode of Ca(2+) uptake (RaM) and a ryanodine receptor (RyR) localized in the inner mitochondrial membrane (IMM). Three subtypes of RyRs have been described and cloned, however, the subtype identity of the mitochondrial ryanodine receptor (mRyR) is unknown. Using subtype specific antibodies, we characterized the mRyR in the IMM from rat heart as RyR1. These results are substantiated by the absence of RyR protein in heart mitochondria from RyR1 knockout mice. The bell-shape Ca(2+)-dependent [(3)H]ryanodine binding curve and its modulation by caffeine and adenylylmethylenediphosphonate (AMPPCP) give further evidence that mRyR functions pharmacologically like RyR1. Ryanodine prevents mitochondrial Ca(2+) uptake induced by raising extramitochondrial Ca(2+) to 10 microM. Similarly, ryanodine inhibits oxidative phosphorylation stimulated by 10 microM extramitochondrial Ca(2+). In summary, our results show that the mRyR in cardiac muscle has similar biochemical and pharmacological properties to the RyR1 in the sarcoplasmic reticulum (SR) of skeletal muscle. These results could also suggest an efficient mechanism by which mitochondria sequesters Ca(2+) via mRyR during excitation-contraction coupling to stimulate oxidative phosphorylation for ATP production to meet metabolic demands. Thus, the mRyR functions as a transducer for excitation-metabolism coupling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
1717
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Type 1 ryanodine receptor in cardiac mitochondria: transducer of excitation-metabolism coupling.
pubmed:affiliation
Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural