Membrane electrical activity elicits inositol 1,4,5-trisphosphate-dependent slow Ca2+ signals through a G beta gamma/phosphatidylinositol 3-kinase gamma pathway in skeletal myotubes

Eltit, JM; Garcia, AA; Hidalgo J.; LIBERONA, JL; Chiong M.; Lavandero S.; Maldonado E.; Jaimovich E.

Abstract

Tetanic electrical stimulation of myotubes evokes a ryanodine receptor-related fast calcium signal, during the stimulation, followed by a phospholipase C/inositol 1,4,5-trisphosphate-dependent slow calcium signal few seconds after stimulus end. L-type calcium channels (Cav 1.1, dihydropyridine receptors) acting as voltage sensors activate an unknown signaling pathway involved in phospholipase C activation. We demonstrated that both G protein and phosphatidylinositol 3-kinase were activated by electrical stimulation, and both the inositol 1,4,5-trisphosphate rise and slow calcium signal induced by electrical stimulation were blocked by pertussis toxin, by a Gβγ scavenger peptide, and by phosphatidylinositol 3-kinase inhibitors. Immunofluorescence using anti-phosphatidylinositol 3-kinase γ antibodies showed a clear location in striations within the cytoplasm, consistent with a position near the I band region of the sarcomere. The time course of phosphatidylinositol 3-kinase activation, monitored in single living cells using a pleckstrin homology domain fused to green fluorescent protein, was compatible with sequential phospholipase Cγ1 activation as confirmed by phosphorylation assays for the enzyme. Co-transfection of a dominant negative form of phosphatidylinositol 3-kinase γ inhibited the phosphatidylinositol 3-kinase activity as well as the slow calcium signal. We conclude that Gβγ/phosphatidylinositol 3-kinase γ signaling pathway is involved in phospholipase C activation and the generation of the slow calcium signal induced by tetanic stimulation. We postulate that membrane potential fluctuations in skeletal muscle cells can activate a pertussis toxin-sensitive G protein, phosphatidylinositol 3-kinase, phospholipase C pathway toward modulation of long term, activity-dependent plastic changes. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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Título según WOS: Membrane electrical activity elicits inositol 1,4,5-trisphosphate-dependent slow Ca2+ signals through a G beta gamma/phosphatidylinositol 3-kinase gamma pathway in skeletal myotubes
Título según SCOPUS: Membrane electrical activity elicits inositol 1,4,5-trisphosphate-dependent slow Ca2+ signals through a Gß?/phosphatidylinositol 3-kinase ? pathway in skeletal myotubes
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 281
Número: 17
Editorial: Elsevier
Fecha de publicación: 2006
Página de inicio: 12143
Página final: 12154
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M511218200
DOI:

10.1074/jbc.M511218200

Notas: ISI, SCOPUS