Depolarization-induced slow calcium transients activate early genes in skeletal muscle cells.
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.
Carrasco
Maria Angélica
MA
Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 6530499, Chile. mcarras@machi.med.uchile.cl
Riveros
Nora
N
Ríos
Juan
J
Müller
Marioly
M
Torres
Francisco
F
Pineda
Jorge
J
Lantadilla
Soledad
S
Jaimovich
Enrique
E
D000818:Animals; D002110:Caffeine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D004791:Enzyme Inhibitors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017781:Genes, Immediate-Early; D016762:Genes, fos; D016758:Genes, jun; D017874:Immediate-Early Proteins; D008564:Membrane Potentials / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D002110:Caffeine; D020928:Mitogen-Activated Protein Kinases; D011188:Potassium; D002118:Calcium