Purinergic Effects on Na,K-ATPase Activity Differ in Rat and Human Skeletal Muscle

Key pointsr From animal models, it is well established that β 2 -adrenergic stimulation increases contractile force, rates of Ca 2+ release and uptake from the sarcoplasmic reticulum, and Na + -K + -ATPase activity of skeletal muscles. However, these effects are unexplored in humans.r Here we report that β 2 -adrenergic stimulation with the high dose selective β 2 -adrenoceptor agonist terbutaline elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps that are associated with enhanced rates of Ca 2+ release and uptake from the sarcoplasmic reticulum in trained men.r However, we also observed that the positive inotropic and lusitropic effects of β 2 -adrenergic stimulation on m. quadriceps were blunted when muscle fatigue developed.r Furthermore, we show that β 2 -adrenergic stimulation counteracts exercise-induced reductions in Na + -K + -ATPase V max (maximum rate of activity) and elevates glycolytic activity during high intensity exercise.r These findings are important for our understanding of the role of β 2 -adreceptor activation in regulation of ion handling and contractile properties of non-fatigued and fatigued skeletal muscles in humans.Abstract The aim of the present study was to examine the effect of β 2 -adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca 2+ release and uptake, and Na + -K + -ATPase activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 males, EXP2, n = 20 males), where β 2 -adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction (MVC) of m. quadriceps was measured, followed by exercise to fatigue at 120% of maximal oxygen uptake (V O 2 ,max ). A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m. quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45 s sprints. Non-fatigued MVCs were 6 ± 3 and 6 ± 2% higher (P < 0.05) with terbutaline than placebo in EXP1 and EXP2, respectively. Furthermore, peak twitch force was 11 ± 7% higher (P < 0.01) with terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to the same levels with terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half-relaxation time was prolonged (P < 0.05) with terbutaline. Rates of SR Ca 2+ release and uptake at 400 nM [Ca 2+ ] were 15 ± 5 and 14 ± 5% (P < 0.05) higher, respectively, with terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na + -K + -ATPase activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in maximum rate of activity (V max ) at time of fatigue. In conclusion, increased contractile force induced by β 2 -adrenergic stimulation is associated with enhanced rate of Ca 2+ release in humans....

Section: Discussionsupporting

confidence: 52%

“…In contrast to our observations, Juel et al . () observed increased Na + –K + ‐ATPase activity at 5 m m Na + in rat and human muscle membranes upon addition of cAMP (1 m m ). However, in that study the Na + –K + ‐ATPase was stimulated by addition of cAMP into the assay in vitro (Juel et al .…”

Section: Discussionmentioning

confidence: 92%

β₂‐Adrenergic stimulation enhances Ca²⁺ release and contractile properties of skeletal muscles, and counteracts exercise‐induced reductions in Na⁺–K⁺‐ATPase V_max in trained men

Hostrup

Kalsen

Ørtenblad

et al. 2014

“…), and reduces Na + –K + pump activity (Juel et al . ). Furthermore, anaerobic energy production through glycolysis leads to lactate − production and the accompanying H + accumulation changes SERCA activity and K ATP channel sensitivity for ATP (Davies, , , Westerblad & Allen, , Xu et al .…”

Section: Introductionmentioning

confidence: 97%

Limitations in intense exercise performance of athletes – effect of speed endurance training on ion handling and fatigue development

Hostrup

Bangsbo

2016

Self Cite

Mechanisms underlying fatigue development and limitations for performance during intense exercise have been intensively studied during the past couple of decades. Fatigue development may involve several interacting factors and depends on type of exercise undertaken and training level of the individual. Intense exercise (½-6 min) causes major ionic perturbations (Ca , Cl , H , K , lactate and Na ) that may reduce sarcolemmal excitability, Ca release and force production of skeletal muscle. Maintenance of ion homeostasis is thus essential to sustain force production and power output during intense exercise. Regular speed endurance training (SET), i.e. exercise performed at intensities above that corresponding to maximum oxygen consumption (V̇O2, max ), enhances intense exercise performance. However, most of the studies that have provided mechanistic insight into the beneficial effects of SET have been conducted in untrained and recreationally active individuals, making extrapolation towards athletes' performance difficult. Nevertheless, recent studies indicate that only a few weeks of SET enhances intense exercise performance in highly trained individuals. In these studies, the enhanced performance was not associated with changes in V̇O2, max and muscle oxidative capacity, but rather with adaptations in muscle ion handling, including lowered interstitial concentrations of K during and in recovery from intense exercise, improved lactate -H transport and H regulation, and enhanced Ca release function. The purpose of this Topical Review is to provide an overview of the effect of SET and to discuss potential mechanisms underlying enhancements in performance induced by SET in already well-trained individuals with special emphasis on ion handling in skeletal muscle.

“…Na + –K + ‐ATPase) (Clausen & Flatman, ; Juel, ; Clausen, ; Juel et al . ). Ouabain, an inhibitor of the Na + –K + pump, antagonizes the ability of adrenaline, β‐agonists or DBcAMP to stimulate net Na + efflux and K + influx, lower intracellular [Na + ] ([Na + ] i ), raise intracellular [K + ] ([K + ] i ), and hyperpolarize the sarcolemma (Clausen & Flatman, ; McArdle & D'Alonzo, ; Clausen, ).…”

Section: Introductionmentioning

confidence: 97%

β‐Adrenergic modulation of skeletal muscle contraction: key role of excitation–contraction coupling

Cairns

Borrani

2015

channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca 2+ pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca 2+ loading of SR may assist force potentiation in fast-twitch muscle. Some human studies show no significant force potentiation which appears to be related to the β-agonist concentration used. Indeed high-dose β-agonists (ß0.1 μM) enhance SR Ca 2+ -release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline/β-agonists influence muscle performance during exercise/stress in humans. PKA, cAMP-dependent protein kinase; PLB, phospholamban; RyR1, skeletal muscle ryanodine receptor; SERCA, Ca 2+ pump; t-tubule, transverse tubule. P indicates phosphorylation site.