The contractile performance of mammalian fast twitch skeletal muscle is history dependent. The effect of previous or ongoing contractile activity to potentiate force, i.e. increase isometric twitch force, is a fundamental property of fast skeletal muscle. The precise manifestation of force potentiation is dependent upon a variety of factors with two general types being identified; staircase potentiation referring to the progressive increase in isometric twitch force observed during low frequency stimulation while posttetanic potentiation refers to the step-like increase in isometric twitch force observed following a brief higher frequency (i.e. tetanic) stimulation. Classic studies established that the magnitude and duration of potentiation depends on a number of factors including muscle fiber type, species, temperature, sarcomere length and stimulation paradigm. In addition to isometric twitch force, more recent work has shown that potentiation also influences dynamic (i.e. concentric and/or isotonic) force, work and power at a range of stimulus frequencies in situ or in vitro, an effect that may translate to enhanced physiological function in vivo. Early studies performed on both intact and permeabilized models established that the primary mechanism for this modulation of performance was phosphorylation of myosin, a modification that increased the Ca(2+) sensitivity of contraction. More recent work from a variety of muscle models indicates, however, the presence of a secondary mechanism for potentiation that may involve altered Ca(2+) handling. The primary purpose of this review is to highlight these recent findings relative to the physiological utility of force potentiation in vivo.

The increase in isometric twitch force observed in fast-twitch rodent muscles during or after activity, known universally as potentiation, is normally associated with myosin regulatory light chain (RLC) phosphorylation. Interestingly, fast muscles from mice devoid of detectable skeletal myosin light chain kinase (skMLCK) retain a reduced ability to potentiate twitch force, indicating the presence of a secondary origin for this characteristic feature of the fast muscle phenotype. The purpose of this study was to assess changes in intracellular cytosolic free Ca2+ concentration ([Ca2+]i) after a potentiating stimulus in mouse lumbrical muscle (37°C). Lumbricals were loaded with the Ca2+-sensitive fluorescent indicators fura-2 or furaptra to detect changes in resting and peak, respectively, intracellular Ca2+ levels caused by 2.5 s of 20-Hz stimulation. Although this protocol produced an immediate increase in twitch force of 17 ± 3% (all data are n = 10) (P < 0.01), this potentiation dissipated quickly and was absent 30 s afterward. Fura-2 fluorescence signals at rest were increased by 11.1 ± 1.3% (P < 0.01) during potentiation, indicating a significant increase in resting [Ca2+]i. Interestingly, furaptra signals showed no change to either the amplitude or the duration of the intracellular Ca2+ transients (ICTs) that triggered potentiated twitches during this time (P < 0.50). Immunofluorescence work showed that 77% of lumbrical fibers expressed myosin heavy chain isoform IIx and/or IIb, but with low expression of skMLCK and high expression of myosin phosphatase targeting subunit 2. As a result, lumbrical muscles displayed no detectable RLC phosphorylation either at rest or after stimulation. We conclude that stimulation-induced elevations in resting [Ca2+]i, in the absence of change in the ICT, are responsible for a small-magnitude, short-lived potentiation of isometric twitch force. If operative in other fast-twitch muscles, this mechanism may complement the potentiating influence of myosin RLC phosphorylation.

Globally, traditional and herbal teas are a prominent dietary source of polyphenols, and represent a class of bioactive molecules that are closely associated with a variety of health benefits. Most consumers prepare tea using tea bags, although there is little information about whether this production step alters the content of the final product. The study purpose was to investigate the effect of steep time and tea type on the polyphenol content and predicted antioxidant capacity of commercially available tea bag products, including Green, Orange Pekoe, Red Roiboos, Peppermint, and Chamomile. Total polyphenol content (TPC), antioxidant capacity (1,1-diphenyl-2-picrylhydrazyl inhibition), and total predicted antioxidant capacity were measured in aliquots sampled every minute for 10 min. Polyphenols were extracted into solution in a nonlinear fashion, with~80-90% of the TPC appearing within 5 min of tea bag immersion. Moreover, a significant range in TPC values was observed between products, with true teas containing at least two-fold greater polyphenol content than the herbal varieties. Our results are consistent with previous work using loose-leaf tea products and demonstrates that tea bag products are an effective source of polyphenols that may offer health benefits relating to their constituent antioxidant activity.

Dunford EC, Herbst EA, Jeoung NH, Gittings W, Inglis JG, Vandenboom R, LeBlanc PJ, Harris RA, Peters SJ. PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation. Am J Physiol Regul Integr Comp Physiol 300: R1487-R1493, 2011. First published March 16, 2011 doi:10.1152/ajpregu.00498.2010.-Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate oxidation in skeletal muscle. PDH is deactivated by a set of PDH kinases (PDK1, PDK2, PDK3, PDK4), with PDK2 and PDK4 being the most predominant isoforms in skeletal muscle. Although PDK2 is the most abundant isoform, few studies have examined its physiological role. The role of PDK2 on PDH activation (PDHa) at rest and during muscle stimulation at 10 and 40 Hz (eliciting low-and moderate-intensity muscle contractions, respectively) in isolated extensor digitorum longus muscles was studied in PDK2 knockout (PDK2KO) and wild-type (WT) mice (n ϭ 5 per group). PDHa activity was unexpectedly 35 and 77% lower in PDK2KO than WT muscle (P ϭ 0.043), while total PDK activity was nearly fourfold lower in PDK2KO muscle (P ϭ 0.006). During 40-Hz contractions, initial force was lower in PDK2KO than WT muscle (P Ͻ 0.001) but fatigued similarly to ϳ75% of initial force by 3 min. There were no differences in initial force or rate of fatigue during 10-Hz contractions. PDK1 compensated for the lack of PDK2 and was 1.8-fold higher in PDK2KO than WT muscle (P ϭ 0.019). This likely contributed to ensuring that resting PDHa activity was similar between the groups and accounts for the lower PDH activation during muscle contraction, as PDK1 is a very potent inhibitor of the PDH complex. Increased PDK1 expression appears to be regulated by hypoxia inducible factor-1␣, which was 3.5-fold higher in PDK2KO muscle. It is clear that PDK2 activity is essential, even at rest, in regulation of carbohydrate oxidation and production of reducing equivalents for the electron transport chain. In addition, these results underscore the importance of the overall kinetics of the PDK isoform population, rather than total PDK activity, in determining transformation of the PDH complex and PDHa activity during muscle contraction. pyruvate dehydrogenase 4; pyruvate dehydrogenase 1; carbohydrate oxidation; hypoxia inducible factor-1␣; E1␣; E2 THE PYRUVATE DEHYDROGENASE (PDH) complex plays a major role in the regulation of glucose homeostasis by catalyzing the decarboxylation of pyruvate to acetyl-CoA. PDH links glycolysis to the tricarboxylic acid (TCA) cycle, as PDH controls carbohydrate oxidation by regulating the entrance of carbohydrate-derived acetyl units into the TCA cycle (10). PDH activation is regulated through reversible phosphorylation and dephosphorylation carried out by intrinsic regulatory enzymes. Sequential phosphorylation of E1 at three specific serine residues, serine 264 (site 1), serine 271 (site 2), and serine 203 (site 3), by a family of PDH kinases (PDK1, PDK2, PDK3, PDK4) renders the complex inactive (42, 43), w...

Consumption of a 13-week HFS diet at 20 weeks of age did not exacerbate age-related declines in bone or muscle, but these tissues do not decline in a coordinate manner with greater declines in bone than muscle.