. Adaptations in human muscle sarcoplasmic reticulum to prolonged submaximal training. J Appl Physiol 94: 2034-2042, 2003; 10.1152/japplphysiol.00244.2002.-In this study, we employed single-leg submaximal cycle training, conducted over a 10-wk period, to investigate adaptations in sarcoplasmic reticulum (SR) Ca 2ϩ -regulatory proteins and processes of the vastus lateralis. During the final weeks, the untrained volunteers (age 21.4 Ϯ 0.3 yr; means Ϯ SE, n ϭ 10) were exercising 5 times/wk and for 60 min/session. Analyses were performed on tissue extracted by needle biopsy ϳ4 days after the last training session. Compared with the control leg, the trained leg displayed a 19% reduction (P Ͻ 0.05) in homogenate maximal Ca 2ϩ -ATPase activity (192 Ϯ 11 vs. 156 Ϯ 18 mol ⅐ g protein Ϫ1 ⅐ min Ϫ1 ), a 4.3% increase (P Ͻ 0.05) in pCa 50, defined as the Ca 2ϩ concentration at half-maximal activity (6.01 Ϯ 0.05 vs. 6.26 Ϯ 0.07), and no change in the Hill coefficient (1.75 Ϯ 0.15 vs. 1.76 Ϯ 0.21). Western blot analysis using monoclonal antibodies (7E6 and A52) revealed a 13% lower (P Ͻ 0.05) sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA) 1 in trained vs. control in the absence of differences in SERCA2a. Training also resulted in an 18% lower (P Ͻ 0.05) SR Ca 2ϩ uptake and a 26% lower (P Ͻ 0.05) Ca 2ϩ release. It is concluded that a downregulation in SR Ca 2ϩ cycling in vastus lateralis occurs with aerobic-based training, which at least in the case of Ca 2ϩ uptake can be explained by reduction in Ca 2ϩ -ATPase activity and SERCA1 protein levels. calcium homeostasis; Ca 2ϩ -ATPase; Ca 2ϩ uptake; Ca 2ϩ release; exercise REGULAR CONTRACTILE ACTIVITY is a potentially potent stimulus for altering the composition, structure, and function of the muscle cell. Nowhere is this more evident than with the chronic low-frequency electrical stimulation (CLFS) model in which contractile activity is characteristically induced for 12-24 h/day over several weeks. Induced patterns of submaximal contractions of this nature typically applied to muscles composed of a predominance of fast-twitch (type II) fibers result in extensive reorganization of both the excitation and contraction processes and the energy metabolic pathways involved in energy supply. Although the magnitude of the adaptations vary, qualitatively similar adaptations appear to occur between species (dog, rat, mouse, rabbit) (29).Despite the fact that the CLFS model has proved invaluable for studying the limits of phenotypic plasticity in skeletal muscle and the factors regulating the expression of a large number of proteins involved in fiber-type transformation, it is nonphysiological (30). In physiological models, voluntary activity is used to elicit training adaptations. Voluntary training typically involves a relatively brief session of exercise followed by a prolonged recovery period, which could last for 2-3 days depending on the training frequency. Moreover, it is not clear how the intracellular signals mediating altered protein expression in CLFS translate into different ...