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dc.creatorFernandez Sada, E.-
dc.creatorSilva Platas, C.-
dc.creatorVillegas, C. A.-
dc.creatorRivero, S. L.-
dc.creatorWillis, B. C.-
dc.creatorGarcía, N.-
dc.creatorGarza, J. R.-
dc.creatorOropeza Almazán, Y.-
dc.creatorValverde, Carlos Alfredo-
dc.creatorMazzocchi, Gabriela-
dc.creatorZazueta, C.-
dc.creatorTorre Amione, G.-
dc.creatorGarcía Rivas, G.-
dc.date2017-01-26T20:18:40Z-
dc.date2017-01-26T20:18:40Z-
dc.date2014-09-
dc.date2017-01-25T13:57:50Z-
dc.date.accessioned2019-04-29T15:40:39Z-
dc.date.available2019-04-29T15:40:39Z-
dc.date.issued2017-01-26T20:18:40Z-
dc.date.issued2017-01-26T20:18:40Z-
dc.date.issued2014-09-
dc.date.issued2017-01-25T13:57:50Z-
dc.identifierFernandez Sada, E.; Silva Platas, C.; Villegas, C. A.; Rivero, S. L.; Willis, B. C.; et al.; Cardiac responses to β-adrenoceptor stimulation is partly dependent on mitochondrial calcium uniporter activity; Wiley; British Journal Of Pharmacology; 171; 18; 9-2014; 4207-4221-
dc.identifier0007-1188-
dc.identifierhttp://hdl.handle.net/11336/12024-
dc.identifier1476-5381-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/299264-
dc.descriptionBackground and Purpose: Despite the importance of mitochondrial Ca2+ to metabolic regulation and cell physiology, little is known about the mechanisms that regulate Ca2+ entry into the mitochondria. Accordingly, we established a system to determine the role of the mitochondrial Ca2+ uniporter in an isolated heart model, at baseline and during increased workload following β-adrenoceptor stimulation. Experimental Approach: Cardiac contractility, oxygen consumption and intracellular Ca2+ transients were measured in ex vivo perfused murine hearts. Ru360 and spermine were used to modify mitochondrial Ca2+ uniporter activity. Changes in mitochondrial Ca2+ content and energetic phosphate metabolite levels were determined. Key Results: The addition of Ru360, a selective inhibitor of the mitochondrial Ca2+ uniporter, induced progressively and sustained negative inotropic effects that were dose-dependent with an EC50 of 7 μM. Treatment with spermine, a uniporter agonist, showed a positive inotropic effect that was blocked by Ru360. Inotropic stimulation with isoprenaline elevated oxygen consumption (2.7-fold), Ca2+-dependent activation of pyruvate dehydrogenase (5-fold) and mitochondrial Ca2+ content (2.5-fold). However, in Ru360-treated hearts, this parameter was attenuated. In addition, β-adrenoceptor stimulation in the presence of Ru360 did not affect intracellular Ca2+ handling, PKA or Ca2+/calmodulin-dependent PK signalling. Conclusions and Implications: Inhibition of the mitochondrial Ca2+ uniporter decreases β-adrenoceptor response, uncoupling between workload and production of energetic metabolites. Our results support the hypothesis that the coupling of workload and energy supply is partly dependent on mitochondrial Ca2+ uniporter activity.-
dc.descriptionFil: Fernandez Sada, E.. Tecnológico de Monterrey; México-
dc.descriptionFil: Silva Platas, C.. Tecnológico de Monterrey; México-
dc.descriptionFil: Villegas, C. A.. Tecnológico de Monterrey; México-
dc.descriptionFil: Rivero, S. L.. Tecnológico de Monterrey; México-
dc.descriptionFil: Willis, B. C.. Tecnológico de Monterrey; México-
dc.descriptionFil: García, N.. Tecnológico de Monterrey; México. Instituto de Cardiología y Medicina Vascular; México-
dc.descriptionFil: Garza, J. R.. Tecnológico de Monterrey; México-
dc.descriptionFil: Oropeza Almazán, Y.. Tecnológico de Monterrey; México-
dc.descriptionFil: Valverde, Carlos Alfredo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina-
dc.descriptionFil: Mazzocchi, Gabriela. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina-
dc.descriptionFil: Zazueta, C.. Instituto Nacional de Cardiología ‘Ignacio Chávez’; México-
dc.descriptionFil: Torre Amione, G.. Tecnológico de Monterrey; México. Instituto de Cardiología y Medicina Vascular; México-
dc.descriptionFil: García Rivas, G.. Tecnológico de Monterrey; México. Instituto de Cardiología y Medicina Vascular; México-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherWiley-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/bph.12684-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/bph.12684/abstract-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectMitochondria-
dc.subjectBiochemical pharmacology-
dc.subjectCatecholamines-
dc.subjectIon channles-
dc.subjectOtras Medicina Básica-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleCardiac responses to β-adrenoceptor stimulation is partly dependent on mitochondrial calcium uniporter activity-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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