Myosin phosphorylation and force potentiation in skeletal muscle: evidence from animal models

Abstract

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.

Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice

“…For soleus muscle, there is minimal potentiation of twitch force (Ͻ10%) elicited by the EDL PTP protocol or variations of that protocol (50,60), and in preliminary experiments we found the same. Because it would be difficult to detect attenuation from this already low level of potentiation, we developed a tetanic potentiation protocol for soleus muscles based on the concept 1) of staircase potentiation (60), only using a higher stimulation frequency to elicit tetanic rather than twitch contractions; 2) that high stimulation frequency is needed to phosphorylate RLC in soleus muscle (37); 3) that soleus muscle is fatigue resistant and can endure repetitive, long-duration stimulations during the potentiating contractions without run down; and the knowledge 4) that stronger stimulus factors such as concentric force and work modulate the extent of potentiation (69).…”

“…In skeletal muscle, pRLC increases the sensitivity of the actin-myosin contractile apparatus to Ca 2ϩ activation, thus enhancing myosin motor function and development of force (23,36,60). Thus, we speculated that E 2 -induced pRLC has a functional impact on contractility.…”

“…Thus, we speculated that E 2 -induced pRLC has a functional impact on contractility. We tested our hypothesis by investigating PTP in isolated skeletal muscles, because pRLC induced the potentiation of force and the rate of force development (14,59,60). Indeed, potentiated force and the maximal rate of force development (ϩdP/dt) were lower in EDL muscles from OVX than in Sham mice.…”

“…3 and 4). The long-term consequence of heightened PTP by E 2 -mediated pRLC is not clear, but because PTP regulates mechanical function of contracting skeletal muscle by augmenting Ca 2ϩ sensitivity of contractile apparatus to increase the development of force, it has been suggested that overall muscle performance could benefit (14,60). Theoretically, the nature of E 2 repetitive fluctuations in females could induce an adaptive response that would benefit muscle performance in the long term, although further studies will need to test this theory.…”

Prolonged activity evokes potentiation and the “sag” phenomenon in slow motor units of rat soleus

“…2C-2D). The latter may, in turn, be related to increased release of calcium ions within these responses caused by the preceding long activity and transient changes in the phosphorylation state of the myosin light chain subunits responsible for twitch potentiation (see Vandenboom et al 2013 for a review).…”