Interactions between sustained contractile activity and β-adrenergic receptors in regulation of gene expression in skeletal muscles

Continuous electrical stimulation for 10-21 days of the motor nerve innervating the anterior compartment muscles of adult rabbits increased both the density of β-adrenergic receptors (β-AR) and tissue concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) by two to threefold. Changes in cAMP and in β-AR occurred in parallel with stimulation-induced adaptations in the specific activity of mitochondrial enzymes (2- to 6-fold increases) and with changes in steady-state concentrations of mitochondrial RNA, β-F1ATPase mRNA, and myoglobin mRNA (2- to 11-fold increases). These increases in muscle cAMP, in β-AR, and in expression of protein and mRNA products of genes encoding proteins of oxidative metabolism occurred even in animals receiving high doses of propranolol during the period of electrical stimulation. In contrast to genes that encode proteins of oxidative metabolism, the direction and the time course of activity-induced changes in expression of the glycolytic enzyme aldolase A appeared to be unrelated to changes in muscle cAMP; suppression of steady-state concentrations of aldolase A mRNA was maximal (20-25% of control) at early time points preceding the maximal rise in cAMP. In addition, administration of propranolol attenuated the suppressive effect of continuous contractile activity on expression of aldolase A, even in the absence of an effect of this drug on cAMP in stimulated muscles. We conclude that activity-induced changes in cAMP, in β-AR, and in expression of genes that encode proteins important for oxidative metabolism occur as a direct consequence of contractile activity and do not require concomitant stimulation of β-AR. Although these findings do not establish a direct causal relationship between cAMP and gene expression in skeletal muscle, they provide a rationale for specific, experimentally testable, hypotheses concerning the role of cAMP in biochemical pathways involved in the effects of endurance training on the oxidative capacity of skeletal muscle fibers.

Duke Scholars

Author William Erle Kraus Medicine, Cardiology