Effects of acidosis and inorganic phosphate on Ca 2+ sensitivity of young and older adult skeletal muscle fibers

The cellular mechanisms for the age-related loss in skeletal muscle contractile function and increased fatigability are unresolved. We previously observed that the depressive effects of fatiguing levels of hydrogen (H + )(pH6.8-6.6-6.2) and inorganic phosphate (P i )(12-20-30mM) did not differ in myofibers from young compared with older adults. However, these studies used saturating Ca 2+ , when fatigue during high-intensity contractions in vivo also likely involves a decrease in myoplasmic free Ca 2+ . Thus, we compared the Ca 2+ sensitivity of myofibers from 10 young (22.1±3.6; 5women) and 13 older (71.7±5.5; 7women) adults in conditions mimicking quiescent (pH7+4mM P i ) and fatigued (pH6.2+30mM P i ) muscle. Fast fiber cross-sectional area was ~35% smaller in older (4,859±2,116μm 2 ) compared with young (7,446±2,399μm 2 , P=0.002), which corresponded with lower maximal absolute force (P o ) in both quiescent (old=0.75±0.30mN; young=1.13±0.32 mN, P=0.002) and fatigue conditions (old=0.35±0.14mN; young=0.52±0.16mN, P=0.002). There were no differences in fast fiber size-specific P o , indicating the age-related decline in force was due to differences in fiber size. Elevated H + and P i shifted the force-pCa relationship to the right, confirming non-human studies that these metabolites contribute to fatigue by depressing the sensitivity of the myofilaments to Ca 2+ . However, Ca 2+ sensitivity was not different with age or sex in either condition, and the metabolite-induced shift in the force-pCa relationship did not differ with age in either the slow (P=0.507) or fast (P=0.115) fibers. These data suggest the age-related increase in fatigability of limb muscles cannot be explained by an increased sensitivity of the myofibers to elevated H + and P i in maximal or submaximal Ca 2+ .