Isoproterenol enhances force production in mouse glycolytic and oxidative muscle via separate mechanisms.

Fight or flight is a biologic phenomenon that involves activation of β-adrenoceptors in skeletal muscle. However, how force generation is enhanced through adrenergic activation in different muscle types is not fully understood. We studied the effects of isoproterenol (ISO, β-receptor agonist) on force generation and energy metabolism in isolated mouse soleus (SOL, oxidative) and extensor digitorum longus (EDL, glycolytic) muscles. Muscles were stimulated with isometric tetanic contractions and analyzed for metabolites and phosphorylase activity. Under conditions of maximal force production, ISO enhanced force generation markedly more in SOL (22%) than in EDL (8%). Similarly, during a prolonged tetanic contraction (30 s for SOL and 10 s for EDL), ISO-enhanced the force × time integral more in SOL (25%) than in EDL (3%). ISO induced marked activation of phosphorylase in both muscles in the basal state, which was associated with glycogenolysis (less in SOL than in EDL), and in EDL only, a significant decrease (16%) in inorganic phosphate (P). ATP turnover during sustained contractions (1 s EDL, 5 s SOL) was not affected by ISO in EDL, but essentially doubled in SOL. Under conditions of maximal stimulation, ISO has a minor effect on force generation in EDL that is associated with a decrease in P, whereas ISO has a marked effect on force generation in SOL that is associated with an increase in ATP turnover. Thus, phosphorylase functions as a phosphate trap in ISO-mediated force enhancement in EDL and as a catalyzer of ATP supply in SOL.