Phosphorylase kinase isozymes and phosphorylase in denervated skeletal muscles

Abstract

The effects of motor denervation on levels of phosphorylase kinase isozymes and phosphorylase were investigated in rat epitrochlearis, hemidiaphragm, and soleus muscles. Amounts of the proteins were measured after quantitative immunoprecipitation and found to be decreased by as much as 70% 2 weeks after denervation. Unexpectedly, denervation had little, if any, effect on the relative proportions of the two phosphorylase kinase isozymes. Phosphorylase and phosphorylase kinase were decreased by essentially the same extent after denervation, and the effects of denervation were comparable in all three muscles. The decreases in these enzymes explain, at least in part, the marked alterations in glycogen metabolism that occur after motor denervation.

Neural regulation of the formation of skeletal muscle phosphorylase kinase holoenzyme in adult and developing rat muscle

“…In confirmation of what had been suggested by previous studies using a variety of approaches [21,31,43], the current investigation demonstrates unambiguously that the expression of skeletal muscle phosphorylase kinase is regulated by neural input. It is further implied by these data that there is close integration in the expression of the catalytic and regulatory subunits of phosphorylase kinase, so that free γ subunit does not arise.…”

“…For the latter, the peroneal nerve was exposed as described, but the incision was closed without injuring the nerve. Contralateral control muscles were not used because phosphorylase levels have been shown to exhibit compensatory change with increased muscle use as a consequence of denervating muscles in the opposite limb [21,22]. All of the sham-operated controls exhibited phosphorylase kinase activity, subunit protein and mRNA levels that were not statistically different from the untreated adult controls.…”

“…Were free γ subunits produced, rapid and unregulated glycogenolysis would ensue. The expression and activity of metabolic pathways in skeletal muscle, however, are, in large part, regulated by its motor nerve [19][20][21]. In the studies presented here, the influence of motor innervation on subunit mRNA expression and translation and the assembly of the phosphorylase kinase holoenzyme has been examined in adult animals following muscle denervation and during re-innervation.…”

Effect of denervation on the expression of glycogen phosphorylase in mouse skeletal muscle

“…The levels of two glycogenolytic enzymes, glycogen phosphorylase and phosphorylase kinase, were investigated in rat epitrochlearis, hemidiaphragm and soleus muscle (muscles of different fibretype compositions) after motor-nerve section. Both enzymes were markedly decreased in the denervated muscles as compared with levels measured in the contralateral control muscles (Lawrence & Smith, 1990). Chronic stimulation of fast-twitch fibres with a frequency pattern characteristic of slow-twitch fibres induces major changes in the enzymes of oxidative and glycolytic energy metabolism, which reflects the adaptive response to the new conditions of use and which results in a marked decrease in phosphorylase levels (Henriksson et al, 1986).…”

“…The intracellular concentration of the enzyme declines in response to denervation in mice (Butler et al, 1985a), chickens (Shackleford & Lebherz, 1981) and rats (Lawrence & Smith, 1990). However, it is not clear whether the decay in phosphorylase levels is elicited via changes in the rate of synthesis and/or degradation of the enzyme.…”