Reduced DHPRα1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis

Muscle Nerve. 2013 Nov;48(5):745-51. doi: 10.1002/mus.23805. Epub 2013 Aug 13.


Introduction: Sepsis often causes diaphragm contractile dysfunction. Dihydropyridine receptors (DHPRα1s and DHPRα1c) and ryanodine receptors (RyR1, RyR2, and RyR3) are essential for excitation-contraction coupling in striated muscles. However, their expression in diaphragm during sepsis have not been explored.

Methods: Eight rats received endotoxin, and 8 more rats received placebo. After 24 hours, 3) diaphragm isometric contractile force was measured. The mRNA and protein levels of DHPRs and RyRs in diaphragm muscles were determined.

Results: Sepsis weakened diaphragm contractile function. The expression levels of DHPRα1s and RyR1 were significantly lower in septic rats than in control rats. The expression levels of DHPRα1c and RyR3 were unaffected by sepsis. RyR2 was undetectable at both mRNA and protein levels in the control and sepsis groups.

Conclusions: Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPRα1s and RyR1, the isoforms of skeletal muscles.

Keywords: DHPR; RyR; diaphragm muscle; excitation-contraction coupling; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type / biosynthesis
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Diaphragm / drug effects
  • Diaphragm / metabolism*
  • Diaphragm / physiopathology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Isometric Contraction / drug effects
  • Isometric Contraction / physiology*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Protein Isoforms / drug effects
  • Protein Isoforms / metabolism
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Rats
  • Ryanodine Receptor Calcium Release Channel / biosynthesis
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sepsis / chemically induced
  • Sepsis / metabolism*
  • Sepsis / physiopathology
  • Shock, Septic / metabolism
  • Shock, Septic / physiopathology


  • Calcium Channels, L-Type
  • Protein Isoforms
  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel