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

Sarah J Blackwood,Abram Katz

doi:10.1007/s00424-019-02304-0

Abstract

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 (Pi). 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 Pi, 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.

Highlights

Fight or flight is an established biologic response to a potentially harmful event or perceived threat to survival [16]
isoproterenol hydrochloride (ISO) resulted in increased forces only at high stimulation frequencies in extensor digitorum longus (EDL) (Fig. 2d); a rundown effect was noted in the control group, especially at the lower stimulation frequencies (Fig. 2c)
The peak ISO effect occurred at low frequencies in both SOL (33.7 ± 8.7% at 20 Hz, Fig. 1g) and EDL (34.4 ± 5.6% at 30 Hz, Fig. 1H), whereas for maximal tetanic contractions, the ISO effect was better maintained in the SOL (22.4 ± 4.8% at 100 Hz) than in the EDL (7.7 ± 1.8% at 150 Hz) (P < 0.01 for SOL vs. EDL)

Summary

Introduction

Fight or flight is an established biologic response to a potentially harmful event or perceived threat to survival [16]. It entails a sympathetic discharge consisting of adrenaline (AD) release from the adrenal medulla (as well as noradrenaline from sympathetic nerves) that affects different organs and pathways in the body. With respect to skeletal muscle, AD binds to β-adrenoceptors and enhances force production in skeletal muscle. Sympathomimetic agents increase force generation via β2 receptors [9]. The mechanism by which sympathomimetic agents enhance muscle performance has not been fully

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