|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2006-6-29
|
|
pubmed:abstractText |
The space between the t-tubule invagination and the sarcoplasmic reticulum (SR) membrane, the dyad, in ventricular myocytes has been predicted to experience very high [Ca2+] for short periods of time during a Ca2+ transient. The dyadic space accommodates many protein kinases responsible for the regulation of Ca2+ handling proteins of the cell. We show in vitro that cAMP-dependent protein kinase (PKA) is inhibited by high [Ca2+] through a shift in the ratio of CaATP/MgATP toward CaATP. We further generate a three-dimensional mathematical model of Ca2+ and ATP diffusion within dyad. We use this model to predict the extent to which PKA would be inhibited by an increased CaATP/MgATP ratio during a Ca2+ transient in the dyad in vivo. Our results suggest that under normal physiological conditions a myocyte paced at 1 Hz would experience up to 55% inhibition of PKA within the cardiac dyad, with inhibition averaging 5% throughout the transient, an effect which becomes more pronounced as the myocyte contractile frequency increases (at 7 Hz, PKA inhibition averages 28% across the dyad throughout the duration of a Ca2+ transient).
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-10082479,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-10390518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-10512809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-10603942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-10830164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-11053140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-11246744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-11463611,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-11805843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-11834711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-11909871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-12401811,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-12944290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-1311325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-1404340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-1404341,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-14514795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-15201147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-15465866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-15790957,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-1621949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-1645727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-1852107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-2537030,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-2553712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-3584144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-6050160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-6318814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-6346892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-7195747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-7272283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-7701323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-7836435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-8118949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-8799895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-9184152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-9357788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-9449319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-9724816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16632511-9725890
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0006-3495
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
91
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
433-43
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:16632511-Adenosine Triphosphate,
pubmed-meshheading:16632511-Animals,
pubmed-meshheading:16632511-Calcium,
pubmed-meshheading:16632511-Calcium Signaling,
pubmed-meshheading:16632511-Computer Simulation,
pubmed-meshheading:16632511-Cyclic AMP,
pubmed-meshheading:16632511-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:16632511-Enzyme Activation,
pubmed-meshheading:16632511-Heart Ventricles,
pubmed-meshheading:16632511-Humans,
pubmed-meshheading:16632511-Models, Biological,
pubmed-meshheading:16632511-Myocardial Contraction,
pubmed-meshheading:16632511-Myocytes, Cardiac,
pubmed-meshheading:16632511-Phosphorylation,
pubmed-meshheading:16632511-Sarcomeres,
pubmed-meshheading:16632511-Sarcoplasmic Reticulum
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
Inhibition of cAMP-dependent protein kinase under conditions occurring in the cardiac dyad during a Ca2+ transient.
|
|
pubmed:affiliation |
Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom. pjones@ucalgary.ca
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
