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dc.contributor.author
Aiba, Takeshi
dc.contributor.author
Hesketh, Geoffrey G.
dc.contributor.author
Liu, Ting
dc.contributor.author
Carlisle, Rachael
dc.contributor.author
Villa-Abrille, María Celeste
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dc.contributor.author
O'Rourke, Brian
dc.contributor.author
Akar, Fadi G.
dc.contributor.author
Tomaselli, Gordon F.
dc.date.available
2018-10-05T16:47:47Z
dc.date.issued
2010-02
dc.identifier.citation
Aiba, Takeshi; Hesketh, Geoffrey G.; Liu, Ting; Carlisle, Rachael; Villa-Abrille, María Celeste; et al.; Na+ channel regulation by Ca2+/calmodulin and Ca 2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes; Oxford University Press; Cardiovascular Research; 85; 3; 2-2010; 454-463
dc.identifier.issn
0008-6363
dc.identifier.uri
http://hdl.handle.net/11336/61762
dc.description.abstract
Aims Calmodulin (CaM) regulates Na+ channel gating through binding to an IQ-like motif in the C-terminus. Ca2+/CaM-dependent protein kinase II (CaMKII) regulates Ca2+ handling, and chronic overactivity of CaMKII is associated with left ventricular hypertrophy and dysfunction and lethal arrhythmias. However, the acute effects of Ca 2+/CaM and CaMKII on cardiac Na+ channels are not fully understood.Methods and results Purified NaV1.5-glutathione-S-transferase fusion peptides were phosphorylated in vitro by CaMKII predominantly on the I-II linker. Whole-cell voltage-clamp was used to measure Na+ current (INa) in isolated guinea-pig ventricular myocytes in the absence or presence of CaM or CaMKII in the pipette solution. CaMKII shifted the voltage dependence of Na+ channel availability by ≈+5 mV, hastened recovery from inactivation, decreased entry into intermediate or slow inactivation, and increased persistent (late) current, but did not change INa decay. These CaMKII-induced changes of Na+ channel gating were completely abolished by a specific CaMKII inhibitor, autocamtide-2-related inhibitory peptide (AIP). Ca2+/CaM alone reproduced the CaMKII-induced changes of INa availability and the fraction of channels undergoing slow inactivation, but did not alter recovery from inactivation or the magnitude of the late current. Furthermore, the CaM-induced changes were also completely abolished by AIP. On the other hand, cAMP-dependent protein kinase A inhibitors did not abolish the CaM/CaMKII-induced alterations of INa function.Conclusion Ca 2+/CaM and CaMKII have distinct effects on the inactivation phenotype of cardiac Na+ channels. The differences are consistent with CaM-independent effects of CaMKII on cardiac Na+ channel gating.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Ca2+/Cam-Dependent Protein Kinase Ii
dc.subject
Calcium
dc.subject
Calmodulin
dc.subject
Na-Channel
dc.subject.classification
Inmunología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Na+ channel regulation by Ca2+/calmodulin and Ca 2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-09-10T16:44:18Z
dc.journal.volume
85
dc.journal.number
3
dc.journal.pagination
454-463
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Oxford
dc.description.fil
Fil: Aiba, Takeshi. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Hesketh, Geoffrey G.. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Liu, Ting. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Carlisle, Rachael. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: O'Rourke, Brian. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Akar, Fadi G.. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Tomaselli, Gordon F.. Johns Hopkins University School of Medicine; Estados Unidos
dc.journal.title
Cardiovascular Research
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1093/cvr/cvp324
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/cardiovascres/article/85/3/454/279796
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