Stress-induced increase in skeletal muscle force requires PKA phosphorylation of the ryanodine receptor

Daniel C. Andersson, Matthew J. Betzenhauser, Steven Reiken, Alisa Umanskaya, Takayuki Shiomi, Andrew R. Marks

College of Physicians and Surgeons of Columbia University, New York, USA

The Journal of Physiology

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)

Produits associés

Publication request

Merci de votre intérêt pour notre gamme de produits et de votre demande pour cette publication qui vous sera envoyée si l'équipe de recherche et la revue le permettent. Notre équipe commerciale vous contactera dans les plus brefs délais.