Key points From animal models, it is well established that ß2-adrenergic stimulation increases contractile force, rates of Ca2+ release and uptake from the sarcoplasmic reticulum, and Na+-K+-ATPase activity of skeletal muscles. However, these effects are unexplored in humans. Here we report that ß2-adrenergic stimulation with the high dose selective ß2-adrenoceptor agonist terbutaline elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps that are associated with enhanced rates of Ca2+ release and uptake from the sarcoplasmic reticulum in trained men. However, we also observed that the positive inotropic and lusitropic effects of ß2-adrenergic stimulation on m. quadriceps were blunted when muscle fatigue developed. Furthermore, we show that ß2-adrenergic stimulation counteracts exercise-induced reductions in Na+-K+-ATPase Vmax (maximum rate of activity) and elevates glycolytic activity during high intensity exercise. These findings are important for our understanding of the role of ß2-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 ß2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca2+ 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 ß2-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 (inline image). 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 Ca2+ release and uptake at 400 nm [Ca2+] 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 (Vmax) at time of fatigue. In conclusion, increased contractile force induced by ß2-adrenergic stimulation is associated with enhanced rate of Ca2+ release in humans. While ß2-adrenergic stimulation elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps, these effects are blunted when muscles fatigue.
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