A single oral glucose load decreases arterial plasma [K+] during exercise and recovery

AIM: We investigated whether acute carbohydrate ingestion reduced arterial potassium concentration ([K(+)]) during and after intense exercise and delayed fatigue. METHODS: In a randomized, double‐blind crossover design, eight males ingested 300 ml water containing 75 g glucose (CHO) or placebo (CON); rested for 60 min, then performed high‐intensity intermittent cycling (HIIC) at 130% [Formula: see text] , comprising three 45‐s exercise bouts (EB), then a fourth EB until fatigue. Radial arterial (a) and antecubital venous (v) blood was sampled at rest, before, during and after HIIC and analyzed for plasma ions and metabolites, with forearm arteriovenous differences (a‐v diff) calculated to assess inactive forearm muscle effects. RESULTS: Glucose ingestion elevated [glucose](a) and [insulin](a) above CON (p = .001), being, respectively, ~2‐ and ~5‐fold higher during CHO at 60 min after ingestion (p = .001). Plasma [K(+)](a) rose during and declined following each exercise bout in HIIC (p = .001), falling below baseline at 5 min post‐exercise (p = .007). Both [K(+)](a) and [K(+)](v) were lower during CHO (p = .036, p = .001, respectively, treatment main effect). The [K(+)](a‐v diff) across the forearm widened during exercise (p = .001), returned to baseline during recovery, and was greater in CHO than CON during EB1, EB2 (p = .001) and EB3 (p = .005). Time to fatigue did not differ between trials. CONCLUSION: Acute oral glucose ingestion, as used in a glucose tolerance test, induced a small, systemic K(+)‐lowering effect before, during, and after HIIC, that was detectable in both arterial and venous plasma. This likely reflects insulin‐mediated, increased Na(+),K(+)‐ATPase induced K(+) uptake into non‐contracting muscles. However, glucose ingestion did not delay fatigue

Na+,K+-ATPase in human skeletal muscle: the effects of glucose and sodium bicarbonate, and determination of cellular localisation via immunofluorescence

The sodium-potassium adenosine triphosphatase enzyme (Na+,K+-ATPase; NKA) is a heterodimeric protein comprising catalytic alpha (α-) and regulatory beta (β-) subunits. It drives active coupled transport of Na+ and K+ ions across the plasma membrane of most eukaryotic cells, including skeletal muscle cells, thereby also contributing to regulation of membrane potential. Tight control of Na+/K+ transport and of NKA is essential to maintaining ion homeostasis, excitability and thus muscle function. This thesis comprises two intervention studies investigating different supplementation protocols whose direct or indirect actions target the NKA in skeletal muscle, with the potential to modulate Na+/K+ homeostasis and enhance exercise performance. The first intervention used acute oral glucose supplementation to elevate endogenous insulin, thereby stimulating skeletal muscle NKA activity and modifying K+ homeostasis, under conditions of rest and intense exercise. The second intervention involved chronic sodium bicarbonate ingestion during training, as induced metabolic alkalosis is expected to increase NKA activity in skeletal muscle and lower circulating K+. The third and final study had a methodological focus using immunofluorescence techniques. This study investigated cellular distribution patterns of the NKA isoforms in human skeletal muscle cells and their localisation, contrasting the plasma membrane and intracellular regions, as well as fibre-type differences

Dissociation between short-term unloading and resistance training effects on skeletal muscle Na+,K+-ATPase, muscle function, and fatigue in humans

Physical training increases skeletal muscle Na+,K+-ATPase content (NKA) and improves exercise performance, but the effects of inactivity per se on NKA content and isoform abundance in human muscle are unknown. We investigated the effects of 23-day unilateral lower limb suspension (ULLS) and subsequent 4-wk resistance training (RT) on muscle function and NKA in 6 healthy adults, measuring quadriceps muscle peak torque; fatigue and venous [K+] during intense one-legged cycling exercise; and skeletal muscle NKA content ([3H]ouabain binding) and NKA isoform abundances (immunoblotting) in muscle homogenates (α1-3, β1–2) and in single fibers (α1–3, β1). In the unloaded leg after ULLS, quadriceps peak torque and cycling time to fatigue declined by 22 and 23%, respectively, which were restored with RT. Whole muscle NKA content and homogenate NKA α1–3 and β1–2 isoform abundances were unchanged with ULLS or RT. However, in single muscle fibers, NKA α3 in type I (−66%, P = 0.006) and β1 in type II fibers (−40%, P = 0.016) decreased after ULLS, with other NKA isoforms unchanged. After RT, NKA α1 (79%, P = 0.004) and β1 (35%, P = 0.01) increased in type II fibers, while α2 (76%, P = 0.028) and α3 (142%, P = 0.004) increased in type I fibers compared with post-ULLS. Despite considerably impaired muscle function and earlier fatigue onset, muscle NKA content and homogenate α1 and α2 abundances were unchanged, thus being resilient to inactivity induced by ULLS. Nonetheless, fiber type-specific downregulation with inactivity and upregulation with RT of several NKA isoforms indicate complex regulation of muscle NKA expression in humans

Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+,K+-ATPase in healthy humans

We investigated whether digoxin lowered muscle Na+,K+-ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak-workrate, 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% VO2peak and 67% VO2peak, 90% VO2peak to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% , fatigue, 3 h after exercise). In DIG, in resting muscle, [3H]-ouabain binding site content (OB-Fab) was unchanged; however, bound-digoxin removal with Digibind revealed total ouabain binding (OB+Fab) increased (8.2%, P = 0.047), indicating 7.6% NKA–digoxin occupancy. Quadriceps muscle strength declined in DIG (−4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+]a were unchanged, whilst [K+]v was lower (P = 0.042) and [K+]a-v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB-Fab was increased at 67% VO2peak (per wet-weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+]a, [K+]v and [K+]a-v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+]a, [K+]v and [K+]a-v were unchanged; with exercise (main effects), plasma [K+]a, [K+]v, [K+]a-v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA–digoxin occupancy, with K+ disturbances and fatiguability unchanged