Intramuscular glycogen phosphorylase inhibition blunts sarcoplasmic reticulum calcium release in skeletal muscle

Intramuscular glycogen is a primary energy source for fuel in skeletal muscle and depletion of glycogen is associated with
exercise-induced fatigue caused by decreased sarcoplasmic reticulum (SR) Ca2+ release. However, it is unknown if acute
pharmacological inhibition of glycogen utilization can cause decreased sarcoplasmic reticulum calcium release without
depleting muscle glycogen content. We hypothesized that inhibiting glycogen phosphorylase activity within the skeletal muscle
using the drug CP-316819 would result in decreased SR Ca2+ release due to decreased localized SR triad [ATP], whereby
decreased [ATP] would inhibit ryanodine receptor opening. Mouse flexor digitorum brevis muscle was enzymatically
dissociated and loaded with Indo-1 to measure myoplasmic free [Ca2+] ([Ca2+]i). Our results indicate that inhibiting glycogen
phosporylase via CP-316819 results in decreased SR calcium release at all stimulation frequencies (15 – 150Hz), it blunted
total SR calcium release assessed with supraphysiological [5mM] caffeine treatment, and it reduced resting [Ca2+]i. These
results may suggest that skeletal muscle utilizes glycogen at a localized level to regulate SR Ca2+ release.