6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2h-pyran-2-one and Muscular-Atrophy

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 Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) 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 Ca(2+) to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca(2+) release channel-mediated Ca(2+) 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 Ca(2+) entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.

Topics: Aging; Anilides; Animals; Caffeine; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Electric Stimulation; Excitation Contraction Coupling; Humans; Male; Mice; Muscle Contraction; Muscle, Skeletal; Muscular Atrophy; Naphthalenes; Nickel; Nifedipine; Phosphodiesterase Inhibitors; Pyrones; Thiadiazoles