Linked Life Data

8092302

Source:http://linkedlifedata.com/resource/pubmed/id/8092302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 2
pubmed:dateCreated
1994-10-19
pubmed:abstractText
Repetitive membrane potential (Em) depolarization from -90 to 0 mV in rabbit and ferret ventricular myocytes induces a facilitation or "staircase" of Ca current (ICa), which is Ca (not Em) dependent and takes several seconds to accumulate and dissipate. That is, ICa at the tenth pulse at 1-2 Hz exceeds that at the first pulse (I10 > I1). The ICa staircase was completely abolished by dialysis with either of two inhibitory peptides of Ca-calmodulin-dependent protein kinase (CaMKII) CaMKII(290-309) and CaMKII(273-302)], implicating this kinase. Inclusion of ATP gamma S in the patch pipette gradually increased ICa but also abolished the staircase implicating phosphorylation. KN-62, a nonpeptide CaMKII inhibitor, reversed the ICa staircase (I1 > I10). However, this effect of KN-62 was largely attributed to a slower recovery from inactivation and a gating shift to more negative Em (not seen with CaMKII peptides). Similar results were obtained with H-89 and staurosporine (inhibitors of adenosine 3',5'-cyclic monophosphate and phospholipid-/Ca-dependent protein kinase, respectively). The reversal of the ICa staircase with H-89 and KN-62 could be prevented by more negative interpulse Em or elevation of extracellular [Ca] (which could counteract changes in channel gating due to a reduction in internal negative surface potential). That is, these kinase inhibitors might decrease phosphorylation at the inner membrane surface. In approximately 30% of the cells studied with H-89 and staurosporine the characteristic kinetic difference in ICa inactivation (faster at I1 than I10) was also diminished. This might be due to a relatively nonspecific inhibition of the same protein kinase inhibited by the CaMKII peptides. We conclude that the Ca-dependent ICa facilitation is due to activation of CaMKII and phosphorylation of a site on or near the Ca channel. KN-62, H-89, and staurosporine shifted ICa gating to more negative potentials and slowed recovery from inactivation, effects that could be due to reduction in phosphorylation at the inner membrane surface. Thus the reversal of the ICa staircase by KN-62, H-89, and staurosporine may not be Ca channel specific.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp..., http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines, http://linkedlifedata.com/resource/pubmed/chemical/KN 62, http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-..., http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/adenosine 5'-O-(3-thiotriphosphate)
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H982-93
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Ca-dependent facilitation of cardiac Ca current is due to Ca-calmodulin-dependent protein kinase.
pubmed:affiliation
Department of Physiology, Loyola University Medical School, Maywood, Illinois 60153.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.