Electrical activity regulates AChR gene expression via JNK, PKCζ and Sp1 in skeletal chick muscle

Abstract

Electrical activity of myotubes represses nicotinic acetylcholine receptor (AChR) gene expression. This effect is mimicked by okadaic acid and blocked by tetrodotoxin (TTX) or staurosporine in cultured myocytes [Altiok et al., EMBO J. 16 (1997) 717–725]. In this study, we investigated the mechanism of this repression. We show that addition of exogenous phospholipase D (PLD) and C inhibits AChR expression in a manner which parallels that of okadaic acid. Furthermore, okadaic acid caused an increase of the threonine phosphorylation of protein kinase Cζ (PKCζ) and activator of transcription factor (ATF2) and a decrease of the phosphorylation of Sp1. All these effects were reversed by staurosporine, and TTX also abolished ATF2 phosphorylation. These data reveal a possible involvement of PLD, c-jun N-terminal kinase, PKCζ and Sp1 in the repression of AChR genes by electrical activity.