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

Our aim is to describe the acute effects of catecholamines/-adrenergic agonists on contraction of non-fatigued skeletal muscle in animals and humans, and explain the mechanisms involved. Adrenaline/-agonists (0.1-30m) generally augment peak force across animal species (positive inotropic effect) and abbreviate relaxation of slow-twitch muscles (positive lusitropic effect). A peak force reduction also occurs in slow-twitch muscles in some conditions. (2)-Adrenoceptor stimulation activates distinct cyclic AMP-dependent protein kinases to phosphorylate multiple target proteins. -Agonists modulate sarcolemmal processes (increased resting membrane potential and action potential amplitude) via enhanced Na+-K+ pump and Na+-K+-2Cl(-) cotransporter function, but this does not increase force. Myofibrillar Ca2+ sensitivity and maximum Ca2+-activated force are unchanged. All force potentiation involves amplified myoplasmic Ca2+ transients consequent to increased Ca2+ release from sarcoplasmic reticulum (SR). This unequivocally requires phosphorylation of SR Ca2+ release channels/ryanodine receptors (RyR1) which sensitize the Ca2+-induced Ca2+ release mechanism. Enhanced trans-sarcolemmal Ca2+ influx through phosphorylated voltage-activated Ca2+ channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca2+ pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca2+ 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 -agonist concentration used. Indeed high-dose -agonists (approximate to 0.1m) enhance SR Ca2+-release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline/-agonists influence muscle performance during exercise/stress in humans.