Acute Skeletal Muscle Contractions Orchestrate Signaling Mechanisms to Trigger Nuclear NFATc1 Shuttling and...

Area of Science:

• Skeletal muscle physiology
• Molecular biology
• Exercise science

Background:

• Calcium (Ca²⁺) is crucial for skeletal muscle function, regulating contractions and cellular signaling.
• Ryanodine receptor 1 (RyR1) phosphorylation (pRyR1Ser²⁸⁴⁰) influences Ca²⁺ oscillations and muscle transcriptional activity.
• While chronic exercise effects on pRyR1Ser²⁸⁴⁰ are known, acute exercise impacts remain understudied.

Purpose of the Study:

• To investigate the molecular mechanisms of RyR1 phosphorylation following acute exercise.
• To examine the association between exercise-induced RyR1 phosphorylation and Ca²⁺-dependent physiological changes in skeletal muscle.

Main Methods:

• Analysis of pRyR1Ser²⁸⁴⁰, RyR1 stabilizers, signaling pathways (PTEN/CaMKII/PKA), and Ca²⁺-sensitive factors (NFATc1, histone H3 modifications).
• Study conducted on rat muscles subjected to a single bout of running (concentric or eccentric contractions).

Main Results:

• Both exercise types significantly elevated pRyR1Ser²⁸⁴⁰ levels and stabilizer dissociation from RyR1.
• Activation of RyR1 phosphorylation signaling cascades (PTEN/CaMKII/PKA) was observed.
• Increased Ca²⁺-dependent NFATc1 nuclear abundance and histone H3 acetylation indicated a novel exercise-induced Ca²⁺ equilibrium.

Conclusions:

• Multiple pathways synergistically modify RyR1 function to regulate skeletal muscle phenotypes.
• Acute exercise rapidly alters RyR1 phosphorylation, impacting downstream Ca²⁺-dependent signaling and epigenetic modifications.