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Stress‐induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor
Author(s) -
Andersson Daniel C.,
Betzenhauser Matthew J.,
Reiken Steven,
Umanskaya Alisa,
Shiomi Takayuki,
Marks Andrew R.
Publication year - 2012
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/jphysiol.2012.237925
Subject(s) - ryanodine receptor , ryr1 , skeletal muscle , medicine , endocrinology , chemistry , muscle contraction , ryanodine receptor 2 , endoplasmic reticulum , calcium , cardiac muscle , biology , biochemistry
Key points• Under conditions of acute adrenergic stress (i.e. fight or flight response), the contractile force of muscle is enhanced, a phenomenon known as inotropy. • The molecular determinant of the inotropic mechanism is poorly understood but involves potentiated release of calcium within the muscle cell. • Here we report that adrenergic receptor‐dependent phosphorylation of a single amino acid in the calcium release channel (ryanodine receptor 1) mediates the increased calcium and force that is seen in the muscle following acute stress. • These findings further our understanding of the molecular mechanisms of muscular force regulation, and the importance for exercise physiology and muscle weakness (dynopenia).Abstract Enhancement of contractile force (inotropy) occurs in skeletal muscle following neuroendocrine release of catecholamines and activation of muscle β‐adrenergic receptors. Despite extensive study, the molecular mechanism underlying the inotropic response in skeletal muscle is not well understood. Here we show that phosphorylation of a single serine residue (S2844) in the sarcoplasmic reticulum (SR) Ca 2+ release channel/ryanodine receptor type 1 (RyR1) by protein kinase A (PKA) is critical for skeletal muscle inotropy. Treating fast twitch skeletal muscle from wild‐type mice with the β‐receptor agonist isoproterenol (isoprenaline) increased RyR1 PKA phosphorylation, twitch Ca 2+ and force generation. In contrast, the enhanced muscle Ca 2+ , force and in vivo muscle strength responses following isoproterenol stimulation were abrogated in RyR1‐S2844A mice in which the serine in the PKA site in RyR1 was replaced with alanine. These data suggest that the molecular mechanism underlying skeletal muscle inotropy requires enhanced SR Ca 2+ release due to PKA phosphorylation of S2844 in RyR1.