Altered cross-bridge function may also affect the
force-[Ca2]i relationship via the complex interaction be-
tween myosin cross-bridge attachment and thin (actin)
filament activation (192), and reduced myofibrillar Ca2
sensitivity is frequently observed in skeletal muscle fa-
tigue (168, 480). Skinned fiber experiments have shown
that increased Pi decreases the myofibrillar Ca2 sensitiv-
ity (301, 314). Intriguingly, the inhibitory effect of Pi on
myofibrillar Ca2 sensitivity was recently shown to be
larger at 30 than at 15°C (124), i.e., opposite to the inhib-
itory effect of Pi on cross-bridge force production at
saturating [Ca2], which is smaller at high temperature
(123). Results from unfatigued CK/ fibers, which dis-
play an increased myoplasmic Pi concentration at rest,
also indicate a Pi
-induced decrease in the myofibrillar
Ca2 sensitivity (106).
In summary, a fatigue-induced increase in Pi can
reduce myofibrillar Ca2 sensitivity, which may a have
large impact on force production in later stages of fatigue
where tetanic [Ca2]i decreases.