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dc.contributor.author Vela, Jorge
dc.contributor.author Pérez Millán, María Inés
dc.contributor.author Becu, Damasia
dc.contributor.author Diaz, Graciela Susana
dc.date.available 2017-10-09T21:02:50Z
dc.date.issued 2007
dc.identifier.citation Vela, Jorge; Pérez Millán, María Inés; Becu, Damasia; Diaz, Graciela Susana; Different kinases regulate activation of voltage-dependent calcium channels by depolarization in GH3 cells; American Physiological Society; American Journal of Physiology-cell Physiology; 293; 3; -1-2007; C951-C959
dc.identifier.issn 0363-6143
dc.identifier.uri http://hdl.handle.net/11336/26294
dc.description.abstract The L-type Ca(2+) channel is the primary voltage-dependent Ca(2+)-influx pathway in many excitable and secretory cells, and direct phosphorylation by different kinases is one of the mechanisms involved in the regulation of its activity. The aim of this study was to evaluate the participation of Ser/Thr kinases and tyrosine kinases (TKs) in depolarization-induced Ca(2+) influx in the endocrine somatomammotrope cell line GH3. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using a spectrofluorometric method with fura 2-AM, and 12.5 mM KCl (K(+)) was used as a depolarization stimulus. K(+) induced an abrupt spike (peak) in [Ca(2+)](i) that was abolished in the presence of nifedipine, showing that K(+) enhances [Ca(2+)](i), preferably activating L-type Ca(2+) channels. H89, a selective PKA inhibitor, significantly reduced depolarization-induced Ca(2+) mobilization in a concentration-related manner when it was applied before or after K(+), and okadaic acid, an inhibitor of Ser/Thr phosphatases, which has been shown to regulate PKA-stimulated L-type Ca(2+) channels, increased K(+)-induced Ca(2+) entry. When PKC was activated by PMA, the K(+)-evoked peak in [Ca(2+)](i), as well as the plateau phase, was significantly reduced, and chelerythrine (a PKC inhibitor) potentiated the K(+)-induced increase in [Ca(2+)](i), indicating an inhibitory role of PKC in voltage-dependent Ca(2+) channel (VDCC) activity. Genistein, a TK inhibitor, reduced the K(+)-evoked increase in [Ca(2+)](i), but, unexpectedly, the tyrosine phosphatase inhibitor orthovanadate reduced not only basal Ca(2+) levels but, also, Ca(2+) influx during the plateau phase. Both results suggest that different TKs may act differentially on VDCC activation. Activation of receptor TKs with epidermal growth factor (EGF) or vascular endothelial growth factor potentiated K(+)-induced Ca(2+) influx, and AG-1478 (an EGF receptor inhibitor) decreased it. However, inhibition of the non-receptor TK pp60 c-Src enhanced K(+)-induced Ca(2+) influx. The present study strongly demonstrates that a complex equilibrium among different kinases and phosphatases regulates VDCC activity in the pituitary cell line GH3: PKA and receptor TKs, such as vascular endothelial growth factor receptor and EGF receptor, enhance depolarization-induced Ca(2+) influx, whereas PKC and c-Src have an inhibitory effect. These kinases modulate membrane depolarization and may therefore participate in the regulation of a plethora of intracellular processes, such as hormone secretion, gene expression, protein synthesis, and cell proliferation, in pituitary cells.
dc.format application/pdf
dc.language.iso eng
dc.publisher American Physiological Society
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject CELL LINE
dc.subject PITUITARY GLAND
dc.subject PROTEIN KINASES
dc.subject ISOQUINOLINES
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Different kinases regulate activation of voltage-dependent calcium channels by depolarization in GH3 cells
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-10-06T18:02:12Z
dc.identifier.eissn 1522-1563
dc.journal.volume 293
dc.journal.number 3
dc.journal.pagination C951-C959
dc.journal.pais Estados Unidos
dc.journal.ciudad Bethesda
dc.description.fil Fil: Vela, Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil Fil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil Fil: Diaz, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.journal.title American Journal of Physiology-cell Physiology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://ajpcell.physiology.org/content/293/3/C951
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1152/ajpcell.00429.2006
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/pmid/17507432


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)