Store-Operated Ca²⁺ Entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca²⁺ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca²⁺ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca²⁺ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca²⁺ release channel-mediated Ca²⁺ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca²⁺ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.