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β‐Adrenergic modulation of skeletal muscle contraction: key role of excitation–contraction coupling
Author(s) -
Cairns Simeon P.,
Borrani Fabio
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270909
Subject(s) - ryanodine receptor , chemistry , medicine , endocrinology , contraction (grammar) , long term potentiation , muscle contraction , skeletal muscle , myofilament , stimulation , phospholamban , endoplasmic reticulum , biophysics , myocyte , receptor , biology , biochemistry
Our aim is to describe the acute effects of catecholamines/β‐adrenergic agonists on contraction of non‐fatigued skeletal muscle in animals and humans, and explain the mechanisms involved. Adrenaline/β‐agonists (0.1–30 μ m ) 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. β 2 ‐Adrenoceptor stimulation activates distinct cyclic AMP‐dependent protein kinases to phosphorylate multiple target proteins. β‐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 Ca 2+ sensitivity and maximum Ca 2+ ‐activated force are unchanged. All force potentiation involves amplified myoplasmic Ca 2+ transients consequent to increased Ca 2+ release from sarcoplasmic reticulum (SR). This unequivocally requires phosphorylation of SR Ca 2+ release channels/ryanodine receptors (RyR1) which sensitize the Ca 2+ ‐induced Ca 2+ release mechanism. Enhanced trans‐sarcolemmal Ca 2+ influx through phosphorylated voltage‐activated Ca 2+ 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 (∼0.1 μ m ) 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.