Aging impairs regulation of ryanodine receptors from extensor digitorum longus but not soleus muscles.

ABSTRACT

INTRODUCTION: Because impaired excitation-contraction coupling and reduced sarcoplasmic reticulum (SR) Ca2+ release may contribute to the age-associated decline in skeletal muscle strength, we investigated the effect of aging on regulation of the skeletal muscle isoform of the ryanodine receptor (RyR1) by physiological channel ligands. METHODS: [3 H]Ryanodine binding to membranes from 8- and 26-month-old Fischer 344 extensor digitorum longus (EDL) and soleus muscles was used to investigate the effects of age on RyR1 modulation by Ca2+ and calmodulin (CaM). RESULTS: Aging reduced maximal Ca2+ -stimulated binding to EDL membranes. In 0.3 µM Ca2+ , age reduced binding and CaM increased binding to EDL membranes. In 300 µM Ca2+ , CaM reduced binding, but the age effect was not significant. Aging did not affect Ca2+ or CaM regulation of soleus RyR1. DISCUSSION: In aged fast-twitch muscle, impaired RyR1 Ca2+ regulation may contribute to lower SR Ca2+ release and reduced muscle function. Muscle Nerve 57 1022-1025, 2018.