Activity regulates the levels of acetylcholine receptor alpha-subunit mRNA in cultured chicken myotubes.

Abstract

In vitro blocking the spontaneous activity of primary cultures of chicken embryo myotubes with tetrodotoxin increases .apprxeq. 2-fold their content in surface acetylcholine receptor. To investigate this effect at the level of gene expression, chicken genomic DNA sequences coding for the acetylcholine receptor .alpha. subunit were isolated and characterized. They were shown to belong to a single-copy, polymorphic gene with at least 2 alleles in the chicken strain utilized. Probes derived from these genomic clones were used to quantitate levels of .alpha.-subunit mRNA. In culture, a 2-day exposure to tetrodotoxin increased these mRNA levels up to 13-fold, a value similar to that observed after denervation of chick leg muscle (.apprxeq. 17-fold). Actin mRNA levels varied little in any of these experiments. The notion that membrane electrical activity affects acetylcholine receptor expression by regulating the accumulation of the corresponding mRNA is supported.