Depolarization induced slow calcium transients activate early genes in skeletal
muscle cells.
Carrasco, Maria Angélica, Nora Riveros, Juan Ríos, Marioly Müller, Francisco Torres,
Jorge Pineda, Soledad Lantadilla, and Enrique Jaimovich.
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
APStracts 10:0054C, 2003.
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 (IP3)
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 IP3
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.
APS Manuscript Number C117-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003