Dynamics of parvalbumin expression in low-frequency-stimulated fast-twitch rat muscle.

Similar to previous observations in rabbit muscle, chronic low-frequency stimulation suppressed parvalbumin expression in fast-twitch muscles of the rat. In extensor digitorum longus and tibialis anterior muscles, parvalbumin mRNA levels steeply declined with apparent half-lives of approximately 26 h and 45 h, respectively. Measurements of parvalbumin synthesis indicated that the reduction in mRNA was immediately transmitted to the level of translation. Relative parvalbumin synthesis rates decayed with an apparent half-life of approximately 60 h. Both the decrease in parvalbumin mRNA and synthesis considerably preceded the decay of parvalbumin protein. Although parvalbumin synthesis had approached zero in 14-day-stimulated muscles, parvalbumin content started to decrease only after some delay (28-day-stimulated muscles still contained 40-50% of their normal parvalbumin content). The lag time between fully suppressed synthesis and the onset of parvalbumin decay, as well as the stability of parvalbumin against tryptic cleavage in the presence of Ca2+ and Mg2+, indicated proteolysis as an important post-translational control of parvalbumin levels. The decrease in parvalbumin mRNA followed a similar time course as that of the mRNA specific to the fast myosin heavy chain HCIIb. After complete suppression, parvalbumin mRNA reached control levels 4 days after cessation of stimulation, which demonstrates the complete reversibility of the stimulation-induced parvalbumin suppression. These results show that a slow motoneuron-like impulse pattern rapidly silences the parvalbumin gene, thus overriding fast-fiber-type-specific programs of gene expression. Due to posttranscriptional regulation and the stability of parvalbumin, this high responsiveness of adult skeletal muscle to altered neuromuscular activity is more conspicuous at the mRNA level than at the protein level.