IP3 receptor function and localization in myotubes: an unexplored Ca2+ signaling pathway in skeletal muscle

16. Powell, J., Carrasco, MA, Adams, DS, Drouet, B, Rios, J, Müller, M, Estrada, M and Jaimovich, E.

Keywords: Skeletal muscle, Tissue culture, Inositol 1,4,5-trisphosphate receptors, Signal transduction, Confocal


We present evidence for an unexplored inositol 1,4,5-trisphosphate-mediated Ca(2+) signaling pathway in skeletal muscle. RT-PCR methods confirm expression of all three known isotypes of the inositol trisphosphate receptor in cultured rodent muscle. Confocal microscopy of cultured mouse muscle, doubly labeled for inositol receptor type 1 and proteins of known distribution, reveals that the receptors are localized to the I band of the sarcoplasmic reticulum, and this staining is continuous with staining of the nuclear envelope region. These results suggest that the receptors are positioned to mediate a slowly propagating Ca(2+) wave that follows the fast Ca(2+) transient upon K(+) depolarization. This slow wave, imaged using fluo-3, resulted in an increase in nucleoplasmic Ca(2+) lasting tens of seconds, but not contraction; the slow wave was blocked by both the inositol trisphosphate receptor inhibitor 2-aminoethoxydiphenyl borate and the phospholipase C inhibitor U-73122. To test the hypothesis that these slow Ca(2+) signals are involved in signal cascades leading to regulation of gene expression, we assayed for early effects of K(+) depolarization on mitogen-activated protein kinases, specifically extracellular-signal related kinases 1 and 2 and the transcription factor cAMP response element-binding protein (CREB). Within 30-60 seconds following depolarization, phosphorylation of both the kinases and CREB was evident and could be inhibited by 2-aminoethoxydiphenyl borate. These results suggest a signaling system mediated by Ca(2+) and inositol trisphosphate that could regulate gene expression in muscle cells.

Más información

Título de la Revista: JOURNAL OF CELL SCIENCE
Volumen: 114
Número: 20
Página de inicio: 3673
Página final: 3683
Idioma: Inglés
Financiamiento/Sponsor: Universidad de Chile
URL: https://journals.biologists.com/jcs/article/114/20/3673/35549/IP3-receptor-function-and-localization-in-myotubes


Notas: ISI