Linked Life Data

15718501

Source:http://linkedlifedata.com/resource/pubmed/id/15718501

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-3-18
pubmed:abstractText
Metabolic inhibition (MI) contributes to contractile failure during cardiac ischemia and systolic heart failure, in part due to decreased excitation-contraction (E-C) coupling gain. To investigate the underlying mechanism, we studied subcellular Ca2+ release patterns in whole cell patch clamped rat ventricular myocytes using two-dimensional high-speed laser scanning confocal microscopy. In cells loaded with the Ca2+ buffer EGTA (5 mmol/L) and the fluorescent Ca2+-indicator fluo-3 (1 mmol/L), depolarization from -40 to 0 mV elicited a striped pattern of Ca2+ release. This pattern represents the simultaneous activation of multiple Ca2+ release sites along transverse-tubules. During inhibition of both oxidative and glycolytic metabolism using carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP, 50 nmol/L) and 2-deoxyglucose (2-DG, 10 mmol/L), there was a decrease in inward Ca2+ current (ICa), the spatially averaged Ca2+ transient, and E-C coupling gain, but no reduction in sarcoplasmic reticulum Ca2+ content. The striped pattern of subcellular Ca2+ release became fractured, or disappeared altogether, corresponding to a marked decrease in the area of the cell exhibiting organized Ca2+ release. There was no significant change in the intensity or kinetics of local Ca2+ release. The mechanism is not fully explained by dephosphorylation of L-type Ca2+ channels, because a similar degree of ICa"rundown" in control cells did NOT result in fracturing of the Ca2+ release pattern. We conclude that metabolic inhibition interferes with E-C coupling by (1) reducing trigger Ca2+, and (2) directly inhibiting sarcoplasmic reticulum Ca2+ release site open probability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
551-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15718501-Aerobiosis, pubmed-meshheading:15718501-Animals, pubmed-meshheading:15718501-Calcium, pubmed-meshheading:15718501-Calcium Channels, L-Type, pubmed-meshheading:15718501-Calcium Signaling, pubmed-meshheading:15718501-Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, pubmed-meshheading:15718501-Cells, Cultured, pubmed-meshheading:15718501-Deoxyglucose, pubmed-meshheading:15718501-Glycolysis, pubmed-meshheading:15718501-Heart Failure, pubmed-meshheading:15718501-Heart Ventricles, pubmed-meshheading:15718501-Ion Transport, pubmed-meshheading:15718501-Microscopy, Confocal, pubmed-meshheading:15718501-Myocardial Ischemia, pubmed-meshheading:15718501-Myocytes, Cardiac, pubmed-meshheading:15718501-Patch-Clamp Techniques, pubmed-meshheading:15718501-Rats, pubmed-meshheading:15718501-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:15718501-Sarcoplasmic Reticulum, pubmed-meshheading:15718501-Sodium, pubmed-meshheading:15718501-Subcellular Fractions
pubmed:year
2005
pubmed:articleTitle
Metabolic inhibition alters subcellular calcium release patterns in rat ventricular myocytes: implications for defective excitation-contraction coupling during cardiac ischemia and failure.
pubmed:affiliation
Department of Medicine, Cardiovascular Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-1679, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural