The sarcoplasmic reticulum and SERCA: a nexus for muscular adaptive thermogenesis.

We are currently facing an "obesity epidemic" worldwide. Promoting inefficient metabolism in muscle represents a potential treatment for obesity and its complications. Sarco(endo)plasmic reticulum (SR) Ca2+-ATPase (SERCA) pumps in muscle are responsible for maintaining low cytosolic Ca2+ concentration through the ATP-dependent pumping of Ca2+ from the cytosol into the SR lumen. SERCA activity has the potential to be a critical regulator of body mass and adiposity given that it is estimated to contribute upwards of 20% of daily energy expenditure. More interestingly, this fraction can be modified physiologically in the face of stressors, such as ambient temperature and diet, through its physical interaction with several regulators known to inhibit Ca2+ uptake and muscle function. In this review, we discuss advances in our understanding of Ca2+-cycling thermogenesis within skeletal muscle, focusing on SERCA and its protein regulators, which were thought previously to only modulate muscular contractility. Novelty ATP consumption by SERCA pumps comprises a large proportion of resting energy expenditure in muscle and is dynamically regulated through interactions with small SERCA regulatory proteins. SERCA efficiency correlates significantly with resting metabolism, such that individuals with a higher resting metabolic rate have less energetically efficient SERCA Ca2+ pumping in muscle (i.e., lower coupling ratio). Futile Ca2+ cycling is a versatile heat generating mechanism utilized by both skeletal muscle and beige fat.

Does postactivation potentiation (PAP) increase voluntary performance?

The transient increase in torque of an electrically evoked twitch following a voluntary contraction is called postactivation potentiation (PAP). Phosphorylation of myosin regulatory light chains is the most accepted mechanism explaining the enhanced electrically evoked twitch torque. While many authors attribute voluntary postactivation performance enhancement (PAPE) to the positive effects of PAP, few actually confirmed that contraction was indeed potentiated using electrical stimulation (twitch response) at the time that PAPE was measured. Thus, this review aims to investigate if increases in voluntary performance after a conditioning contraction (CC) are related to the PAP phenomenon. For this, studies that confirmed the presence of PAP through an evoked response after a voluntary CC and concurrently evaluated PAPE were reviewed. Some studies reported increases in PAPE when PAP reaches extremely high values. However, PAPE has also been reported when PAP was not present, and unchanged/diminished performance has been identified when PAP was present. This range of observations demonstrates that mechanisms of PAPE are different from mechanisms of PAP. These mechanisms of PAPE still need to be understood and those studying PAPE should not assume that regulatory light chain phosphorylation is the mechanism for such enhanced voluntary performance. Novelty The occurrence of PAP does not necessarily mean that the voluntary performance will be improved. Improvement in voluntary performance is sometimes observed when the PAP level reaches extremely high values. Other mechanisms may be more relevant than that for PAP in the manifestation of acute increases in performance following a conditioning contraction.