Heavy-load and low-load blood flow restricted resistance training increases Na/K-ATPase subunit but not ClC-1 expression in untrained human skeletal muscle

Abstract Contractile function of skeletal muscle relies on the ability of muscle fibers to trigger and propagate action potentials (APs). These electrical signals are created by transmembrane ion transport through ion channels and membrane transporter systems. In this regard, the Cl- ion channel 1 (ClC-1) and the Na+/K--ATPase (NKA) are central for maintaining ion homeostasis across the sarcolemma during repetitive AP firing inherent of intense contractile activity. Therefore, this randomized controlled trial (RCT) aimed to investigate the changes in ClC-1 and specific NKA subunit isoform expression in response to 6 weeks (18 training sessions) of heavy-load resistance exercise (HLRE) and low-load blood flow restricted resistance exercise (BFRRE), respectively. Also, the potential associations between protein expression and contractile performance were investigated. We show that muscle ClC-1 abundance was not affected by either exercise modality, whereas NKA subunit isoforms 𝛼2 and 𝛽1 increased appx. 80-90% with BFRRE (p<0.05) and 70-80% with HLRE (p<0.05). No differential impact between exercise modalities was observed. At baseline, ClC-1 protein expression correlated inversely with dynamic knee extensor strength (r=-0.365, p=0.04). No correlation was observed between NKA subunit content and contractile performance at baseline. However, training-induced changes in NKA 𝛼2 subunit (r=0.603, p<0.01) and 𝛽1 subunit (r=0.453, p<0.05) correlated with changes in maximal voluntary contraction. These results suggest that the initial adaptation to resistance exercise does not involve changes in ClC-1 abundance in untrained skeletal muscle.