title: Intense resistance exercise induces early and transient increases in ryanodine receptor 1 phosphorylation in human skeletal muscle.
abstract: BACKGROUND
  While ryanodine receptor 1 (RyR1) critically contributes to skeletal muscle contraction abilities by mediating Ca²⁺ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK) senses contraction-induced energetic stress by phosphorylation at Thr¹⁷². Phosphorylation of RyR1 at serine²⁸⁴³ (pRyR1Ser²⁸⁴³) results in leaky RyR1 channels and impaired Ca²⁺homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca²⁺-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise.
  
  
  OBJECTIVE
  Determine the effects and early time-course of resistance exercise on pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² in type I and II myofibers.
  
  
  METHODS
  7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg) performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² levels were determined by western blot and semi-quantitative immunohistochemistry techniques.
  
  
  RESULTS
  While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser²⁸⁴³ increased 15 min and peaked 30 min (p<0.01) post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser²⁸⁴³ levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05). pAMPKThr¹⁷² also increased 15 to 30 min post exercise (p<0.01) in type I and II myofibers and in whole skeletal muscle.
  
  
  CONCLUSIONS
  Resistance exercise induces acutely increased pRyR1Ser²⁸⁴³ and concomitantly pAMPKThr¹⁷² levels for up to 30 min in resistance exercised myofibers. This provides a time-course by which pRyR1Ser²⁸⁴³ can mechanistically impact Ca²⁺handling properties and consequently induce reduced myofiber contractility beyond immediate fatiguing mechanisms.
authors.affiliation: Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, Germany. Gehlert@dshs-koeln.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gehlert
authors.forename: Gerd
authors.initials: G
authors.lastname: Bungartz
authors.forename: Lena
authors.initials: L
authors.lastname: Willkomm
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Korkmaz
authors.forename: Kurt
authors.initials: K
authors.lastname: Pfannkuche
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schiffer
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Frank
authors.initials: F
authors.lastname: Suhr
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D055070:Resistance Training; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D010750:Phosphoproteins; D019837:Ryanodine Receptor Calcium Release Channel; D013912:Threonine; D055372:AMP-Activated Protein Kinases