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Mechanical stretch increases L-type calcium channel stability in cardiomyocytes through a polycystin-1/AKT-dependent mechanism

Authordc.contributor.authorCórdova, Andrés 
Authordc.contributor.authorOlmedo, Ivonne 
Authordc.contributor.authorRiquelme, J. 
Authordc.contributor.authorBarrientos, G. 
Authordc.contributor.authorSánchez, G. 
Authordc.contributor.authorGillette, Thomas G. 
Authordc.contributor.authorLavandero González, Sergio 
Authordc.contributor.authorChiong Lay, Mario 
Authordc.contributor.authorDonoso, P. 
Authordc.contributor.authorPedrozo Cibils, Zully 
Admission datedc.date.accessioned2018-07-23T20:42:28Z
Available datedc.date.available2018-07-23T20:42:28Z
Publication datedc.date.issued2018
Cita de ítemdc.identifier.citationBBA - Molecular Cell Research 1865 (2018) 289–296es_ES
Identifierdc.identifier.other10.1016/j.bbamcr.2017.11.001
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/150173
Abstractdc.description.abstractThe L-type calcium channel (LTCC) is an important determinant of cardiac contractility. Therefore, changes in LTCC activity or protein levels could be expected to affect cardiac function. Several studies describing LTCC regulation are available, but only a few examine LTCC protein stability. Polycystin-1 (PC1) is a mechanosensor that regulates heart contractility and is involved in mechanical stretch-induced cardiac hypertrophy. PC1 was originally described as an unconventional Gi/o protein-coupled receptor in renal cells. We recently reported that PC1 regulates LTCC stability in cardiomyocytes under stress; however, the mechanism underlying this effect remains unknown. Here, we use cultured neonatal rat ventricular myocytes and hypo-osmotic stress (HS) to model mechanical stretch. The model shows that the Cav beta 2 subunit is necessary for LTCC stabilization in cardiomyocytes during mechanical stretch, acting through an AKT-dependent mechanism. Our data also shows that AKT activation depends on the G protein-coupled receptor activity of PC1, specifically its G protein-binding domain, and the associated G beta gamma subunit of a heterotrimeric Gi/o protein. In fact, over-expression of the human PC1 C-terminal mutant lacking the G protein-binding domain blunted the AKT activation-induced increase in Cav1.2 protein in cardiomyocytes. These findings provide novel evidence that PC1 is involved in the regulation of cardiac LTCCs through a Gi beta gamma-AKT-Cav beta 2 pathway, suggesting a new mechanism for regulation of cardiac function.es_ES
Patrocinadordc.description.sponsorshipFondo Nacional de Desarrollo Cientifico y Tecnologico, FONDECYT 1150887 1130407 1160704 Postdoctoral FONDECYT 3140449 3160298 FONDAP 15130011es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherElsevier Science BVes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
Sourcedc.sourceBiochimica et Biophysica Acta-molecular Cell Researches_ES
Keywordsdc.subjectHeartes_ES
Keywordsdc.subjectNeonatal rat ventricular myocyteses_ES
Keywordsdc.subjectCav1.2es_ES
Keywordsdc.subjectCav betaes_ES
Keywordsdc.subjectG-protein coupled receptores_ES
Títulodc.titleMechanical stretch increases L-type calcium channel stability in cardiomyocytes through a polycystin-1/AKT-dependent mechanismes_ES
Document typedc.typeArtículo de revistaes_ES
Catalogueruchile.catalogadorrgfes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES


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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile