Low-load blood flow restriction training and ischemia modulate expression of Na+,K+-ATPase and FXYDs in human skeletal muscle

Anterior cruciate ligament (ACL) rupture leads to muscle deconditioning and downregulation of Na+,K+-ATPase (NKA). Low-load blood flow restriction (LL-BFR) training was shown to improve muscle function after ACL injury, but its effects on NKA are unknown. We analysed expression of NKA and its FXYD regulators in knee muscles from ACL-injured subjects undergoing LL-BFR, low-load training with sham blood flow restriction (LL-Sham), or no training (Control). Additionally, we dissected effects of ischemia components by subjecting cultured human myotubes to glucose deprivation and/or hypoxia. The LL-BFR group had higher vastus lateralis mRNA levels of NKA1, NKA{beta}3, and FXYD5 than the LL-Sham group. In vitro, NKA1, NKA{beta}1, and NKA{beta}3 mRNA and NKA1 and NKA{beta}1 protein levels were downregulated by sustained ischemia and glucose deprivation, but not hypoxia, while FXYD5 protein was upregulated by glucose deprivation. Conversely, intermittent ischemia had no effect on NKA or FXYD expression. In conclusion, our study shows that LL-BFR training induces specific transcriptional adaptations in vastus lateralis after ACL injury, potentially contributing to functional improvements. Moreover, it shows that glucose availability plays a major role in modulating NKA and FXYD expression in muscle cells under ischemic conditions. NEW & NOTEWORTHYO_LIThis is the first study exploring effects of low-load BFR training on Na+,K+-ATPase (NKA) and FXYD expression in knee muscles after anterior cruciate ligament injury. C_LIO_LIEffects of ischemia components were analysed by subjecting cultured human myotubes to glucose deprivation and/or hypoxia. C_LIO_LILL-BFR training induces specific transcriptional adaptations in vastus lateralis after ACL injury, potentially contributing to functional improvements. C_LIO_LIGlucose plays a major role in modulating NKA and FXYD expression in cultured myotubes under ischemic conditions. C_LI