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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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