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

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.

Skeletal muscle thermogenesis induction by exposure to predator odor

“…Our data do not speak to the mechanisms that confer resistance to fatigue; existing evidence supports muscle (Sopariwala et al, 2015) and central (Zaretsky et al, 2018) mechanisms that promote fatigue resistance or endurance capacity, some of which overlap with central mechanisms of predator threat and SNS outflow (Fujikawa et al, 2016;Guimarães et al, 2013;Kunwar et al, 2015;Lindberg et al, 2013;Perez-Gomez et al, 2015;Silva et al, 2013). The mediating role of the SNS is consistent with the known ability of β-adrenergic receptor agonists to facilitate skeletal muscle force production and delay fatigue (Blackwood and Katz, 2019). The overlap between processes modulating thermogenesis or cold adaptation, muscle performance and cost of transport (Schaeffer et al, 2001(Schaeffer et al, , 2005 prompts us to speculate that the underlying thermogenic mechanisms may have been co-opted depending on the selective forces at play (i.e.…”

Role of nitration in control of phosphorylase and glycogenolysis in mouse skeletal muscle

“…There was also a large increase in glucose 6-P in both muscle groups exposed to ONOO -, likely due to an activation of glucose transport (i.e., translocation of GLUT4 transporters) owing to oxidative/metabolic stress and/or direct effects of ONOOon glucose transporters (13)(14)(15)42). Interestingly, lactate and malate (whose increase reflects an activation of mitochondrial respiration (4,46)) decreased substantially in both EDL and soleus muscles.…”

“…In these calculations, it is assumed that during short term intense contractions all lactate production is from glycogen and there is no loss of lactate into the medium (18). Under such conditions, the absolute changes in glycogen are relatively small and will therefore not reflect glycogenolysis as accurately as the changes in glycogenlytic intermediates (4,18).…”

The conventional isoproterenol-induced heart failure model does not consistently mimic the diaphragmatic dysfunction observed in patients

“…Moreover, when investigated in different experimental settings other than the HF model, isoproterenol increased canine and rodent diaphragm contractibility [ 12 – 14 ]. It is interesting to note that isoproterenol may also increase the contractile force of skeletal muscles, as it has been reported when added to the bath of ex vivo preparations of mouse soleus and extensor digitorum longus [ 10 , 11 ]. However, whether continuous chronic infusion of isoproterenol as in the HF mouse model induces enhancement of skeletal muscle contractibility is unknown.…”

“…It is noteworthy, however, that there are no data describing whether this widely used HF model results in diaphragm dysfunction. Nevertheless, indirect data from research in other fields where isoproterenol is applied at different doses and modes suggest that this agent elicits an increase in the contractile performance of skeletal muscles [ 10 , 11 ] and in particular of the diaphragm. For instance, it was observed that intravenous injection of isoproterenol enhanced contractility of canine diaphragm [ 12 ].…”