In skeletal muscle, rapidly generated calcium signals trigger muscle contraction. However, calcium signaling is not so simple, there is a second, slower, more complex component that can be observed in cultured cells stimulated with high concentrations of K+. Confocal analysis of the calcium transients induced by high K+ showed the rapid calcium transient in the cytosol and a second delayed calcium transient occurring in the nucleus. Powell et al. show that inositol 3-phosphate receptors (IP3Rs) are expressed in cultured myotubes and that the IP3Rs are distributed along a section of the endoplasmic reticulum that is contiguous with the nuclear membrane. Treatment of cells with either a phospholipase C inhibitor or an IP3R inhibitor blocked the slow calcium signal induced by high K+. Furthermore, stimulated myotubes exhibit an activation of the mitogen-activated protein kinases, ERK1 and ERK2, and increased phosphorylation of the transcription factor CREB. These responses were blocked by treatment of the cells with the IP3R antagonist. Thus, IP3R on the nuclear membrane may be responsible for a nuclear calcium signal that regulates gene expression in stimulated muscles.
J. A. Powell, M. A. Carrasco, D. S. Adams, B. Drouet, J. Rios, M. Müller, M. Estrada, E. Jaimovich, IP3 receptor function and localization in myotubes: An unexplored Ca2+ signaling pathway in skeletal muscle. J. Cell Sci. 114, 3673-3683 (2001). [Online Journal]