Question

You have fatigued your muscles and your ryanodine receptors have started to leak Ca2+ out of the sarcoplasmic reticulum. As a result your muscles will

a. fail to propagate action potentials

b. relax incompletely and slowly

c. generate more force when they contract

d. generate force more efficiently (use less ATP for a given movement)

Answer 1

A)fails to propagate action potential

D)generate force more efficiently (use less ATP for a given movement)

During muscle contraction, membrane depolarization activates voltage-sensing Ca2+ channels in the transverse tubules (Cav1.1) that in turn activate the sarcoplasmic reticulum (SR) Ca2+ release channel, ryanodine receptor 1 (RyR1). The subsequent rise in cytoplasmic [Ca2+]cyt is critical for activation of actin-myosin cross-bridging, shortening of the sarcomere and muscle contraction. The RyR1 is a homotetrameric macromolecular protein complex that includes four RyR1 monomers (∼565,000 Da each), the RyR1 channel-stabilizing subunit calstabin1 (FK506 binding protein 12, FKBP12), kinases, a phosphatase (PP1), phosphodiesterase (PDE4D3), and calmodulin. Moreover, maladaptive cAMP-dependent protein kinase A (PKA)-mediated phosphorylation and redox-dependent modifications (cysteine-nitrosylation and oxidation) of the RyR1 have been linked to impaired Ca2+handling and contractile dysfunction in chronic muscle fatigue, heart failure and muscular dystrophy. Defective SR Ca2+ release has been reported in age-dependent muscle weakness and maladaptive modifications of the RyR1 macromolecular complex have been implicated in this condition. However, the mechanism underlying impaired SR Ca2+ release in aging muscle remains to be elucidated.