Linked Life Data

8544125

Source:http://linkedlifedata.com/resource/pubmed/id/8544125

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1996-2-13
pubmed:abstractText
1. The regulation of the cardiac Ca2+ release channel-ryanodine receptor (RyR) by exogenous acid phosphatase (AcPh) and purified Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) was studied in swine and rabbit sarcoplasmic reticulum (SR) vesicles using [3H]ryanodine binding and planar bilayer reconstitution experiments. 2. Addition of AcPh (1-20 U ml-1) to a standard incubation medium increased [3H]ryanodine binding in a Ca(2+)-dependent manner. Stimulation was only readily apparent in media containing micromolar Ca2+ concentrations. 3. Scatchard analysis of [3H]ryanodine binding curves revealed that AcPh enhanced binding by increasing the affinity of the receptor for [3H]ryanodine without recruiting additional receptor sites (Kd, 9.8 +/- 0.85 and 3.9 +/- 0.65 nM; Bmax (the maximal receptor density), 1.45 +/- 0.14 and 1.47 +/- 0.12 pmol mg-1 for control and AcPh, respectively). The failure of AcPh to increase Bmax suggested that the number of receptors that were 'dormant' due to phosphorylation in the SR preparation was very small. 4. At the single channel level, AcPh increased the open probability (Po) of RyR channels by increasing the opening rate and inducing the appearance of a longer open state while having no effect on single channel conductance. Thus AcPh acted directly on RyR channels or a closely associated regulatory protein. 5. CaMKII decreased both [3H]ryanodine binding and Po of RyRs when added to medium supplemented with micromolar levels of Ca2+ and calmodulin (CaM). Addition of a synthetic peptide inhibitor of CaMKII, or replacement of ATP with the non-hydrolysable ATP analogue adenylyl[beta, gamma-methylene]-diphosphate (AMP-PCP), prevented CaMKII inhibition of RyRs, suggesting that CaMKII acted specifically through a phosphorylation mechanism. 6. The inhibition of RyR channel activity by CaMKII was reversed by the addition of AcPh. Thus we showed that an in vitro phosphorylation-dephosphorylation mechanism effectively regulates RyRs. 7. The results suggest that intracellular signalling pathways that lead to activation of CaMKII may reduce efflux of Ca2+ from the SR by inhibition of RyR channel activity. The Ca2+ dependence of CaMKII inhibition suggests that the role of the phosphorylation mechanism is to modulate the RyR response to Ca2+.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1279096, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1311325, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1331089, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1331805, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1334225, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1334561, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1349013, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1645727, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1655775, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1849885, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-1872369, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2166564, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2173135, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2298749, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2380170, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2434490, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2436032, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2445748, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2446391, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2448641, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2459298, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2475607, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2543067, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2849609, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-2991255, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-3355834, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-3754148, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-6203912, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-6313949, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-6796647, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-7858121, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-8055547, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-8235594, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-8257417, http://linkedlifedata.com/resource/pubmed/commentcorrection/8544125-8390976
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3751
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
487 ( Pt 3)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-22
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Modulation of cardiac ryanodine receptors of swine and rabbit by a phosphorylation-dephosphorylation mechanism.
pubmed:affiliation
Department of Physiology, University of Maryland Medical School, Baltimore 21201, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't