Depolarization-induced slow calcium transients activate early genes in skeletal muscle cells

• Published in: American Journal of Physiology: Cell Physiology Vol. 284; no. 6; pp. C1438 - C1447
• Main Authors: Carrasco, Maria Angelica, Riveros, Nora, Rios, Juan, Muller, Marioly, Torres, Francisco, Pineda, Jorge, Lantadilla, Soledad, Jaimovich, Enrique
• Format: Journal Article
• Language: English
• Published: United States 01.06.2003
• Subjects: Animals; Caffeine - metabolism; Calcium - metabolism; Cells, Cultured; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; DNA-Binding Proteins; Early Growth Response Protein 1; Enzyme Inhibitors - metabolism; Gene Expression Regulation, Developmental; Genes, fos; Genes, Immediate-Early; Genes, jun; Immediate-Early Proteins; Membrane Potentials - physiology; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; Phosphorylation; Potassium - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Signal Transduction - physiology; Transcription Factors; Transcriptional Activation
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00117.2002

Instituto de Ciencias Biomédicas and Centro Fondo de Investigación Avanzada en Areas Prioritarias de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, Santiago 6530499, Chile The signaling mechanisms by which skeletal muscle electrical activity leads to changes in gene expression remain largely undefined. We have reported that myotube depolarization induces calcium signals in the cytosol and nucleus via inositol 1,4,5-trisphosphate (IP 3 ) and phosphorylation of both ERK1/2 and cAMP-response element-binding protein (CREB). We now describe the calcium dependence of P-CREB and P-ERK induction and of the increases in mRNA of the early genes c- fos , c- jun , and egr -1. Increased phosphorylation and early gene activation were maintained in the absence of extracellular calcium, while the increase in intracellular calcium induced by caffeine could mimic the depolarization stimulus. Depolarization performed either in the presence of the IP 3 inhibitors 2-aminoethoxydiphenyl borate or xestospongin C or on cells loaded with BAPTA-AM, in which slow calcium signals were abolished, resulted in decreased activation of the early genes examined. Both early gene activation and CREB phosphorylation were inhibited by ERK phosphorylation blockade. These data suggest a role for calcium in the transcription-related events that follow membrane depolarization in muscle cells. myotubes; signal transduction; inositol 1,4,5-trisphosphate