Effects of elevated H+ and Pi on the force-pCa relationship of skeletal muscle fibers from young and older adults
Authors: Zepeda Carlos , Teigen Laura , Fitts Robert , Hunter Sandra , Sundberg Christopher 
Published: May 2023

Introduction: The cellular mechanisms for the increased fatigability of older adults during dynamic contractions are not well understood. We recently observed that the depressive effects of fatiguing levels of acidosis (H+: pH 6.2) and inorganic phosphate (Pi: 30 mM) did not differ in skeletal muscle fibers from young compared with older adults. However, these studies were conducted in saturating Ca2+ conditions, and fatigue during high-intensity contractions in vivo likely also involves a decrease in myoplasmic free Ca2+ to submaximal levels. No studies have investigated the effects of elevated H+ and Pi on myofilament Ca2+ sensitivity in human skeletal muscle or tested whether the effects of these metabolites in submaximal Ca2+ are altered with aging. Purpose: To 1) determine the effects of elevated H+ and Pi on the force-pCa relationship of human skeletal muscle fibers and 2) test whether the sensitivity of the myofilaments to Ca2+ under conditions mimicking quiescent (pH 7.0 + 4 mM Pi) and fatiguing levels of acidosis and Pi (pH 6.2 + 30 mM Pi) is altered with aging. Methods: Ca2+ sensitivity of chemically permeabilized muscle fibers ( n = 182; 73 myosin heavy chain (MyHC) I and 109 MyHC II) obtained from the vastus lateralis were compared between 4 young (20-21 yrs) and 4 older women (69-77 yrs) in conditions mimicking quiescent (pH 7 + 4 mM Pi) and fatigued muscle (pH 6.2 + 30 mM Pi). Results: There were no differences in Ca2+ sensitivity in either the MyHC I or II fibers between young and older adults, as indicated by the lack of an age difference in pCa50 in the quiescent (MyHC I: young=5.92±0.02, old=5.91±0.02, p=0.756; MyHC II: young=5.99±0.02, old=6.05±0.02, p=0.251) and the fatigue-mimicking condition (MyHC I: young=5.28±0.01, old=5.27±0.01, p=0.571; MyHC II: young=5.32±0.02, old=5.32±0.01, p=0.915). Additionally, no age differences were observed in the activation thresholds or thick filament cooperativity ( n 2 determined by the slope of the force-pCa relationship below pCa50) in either fiber type or condition. The fatigue-mimicking condition caused marked reductions in isometric force in maximal Ca2+ (~54-58%, p<0.001) and decreased the sensitivity of the myofilaments to Ca2+ in both fiber types (~0.64-0.73 pCa units, p<0.001), but the depressive effects of the metabolites did not differ in the fibers between young and older adults (MyHC I: p=0.970; MyHC II: p=0.218). Conclusions: These preliminary data suggest that the sensitivity of the myofilaments to Ca2+ is preserved with aging, and that the age-related increase in fatigability of limb muscles cannot be explained by an increased sensitivity of the muscle fibers to elevated H+ and Pi in maximal or submaximal Ca2+. Supported by NIA R01 grant (AG048262) to CWS, SKH, and RHF. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.