Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Metabolism
Motor control
Neurodegeneration
Cross-disciplinary subjects
Muscular system
General activity
Mood Disorders
Other disorders
Joints
Central Nervous System (CNS)
Sensory system
Authors
Daniel C. Andersson, Matthew J. Betzenhauser, Steven Reiken, Alisa Umanskaya, Takayuki Shiomi, Andrew R. Marks
Lab
College of Physicians and Surgeons of Columbia University, New York, USA
Journal
The Journal of Physiology
Abstract
Enhancement of contractile force (inotropy) occurs in skeletal muscle following neuro-endocrine release of catecholamines and activation of muscle ?-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) Ca2+ release channel/ryanodine receptor type 1 (RyR1) by cAMP-dependent protein kinase A (PKA) is critical for skeletal muscle inotropy. Treating fast-twitch skeletal muscle from wild type mice with the ?-receptor agonist isoproterenol (ISO) increased RyR1 PKA phosphorylation, twitch Ca2+ and force generation. In contrast, the enhanced muscle Ca2+, force and in vivo muscle strength responses following ISO 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 Ca2+ release due to PKA phosphorylation of Serine 2844 in RyR1.
BIOSEB Instruments Used:
Grip strength test (BIO-GS3)
