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

Abstract

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

Slowed relaxation of diaphragm in septic rats is associated with reduced expression of sarco‐endoplasmic reticulum CA2+‐ATPase genes SERCA1 and SERCA2

“…33 The effects of sepsis on mRNA expression and protein content of all 3 RyR subtypes in the diaphragm have been previously explored in detail in a model of endotoxemia 3 and were not our main focus; therefore, in this study, we only assessed changes of the total RyR protein content during sepsis. Based on previous research, RyR1 is the predominant subtype in adult murine diaphragm muscles, 34 RyR2 is absent under both normal and septic conditions, 3 and RyR3 only accounts for 3% of the total RyR. 34 Moreover, the small amount of RyR3 is not altered by sepsis 3 and does not affect diaphragm contractility.…”

“…Sepsis, a systemic inflammatory response to infection, often causes acute lung injury and respiratory failure . The diaphragm is often severely injured during sepsis, resulting in respiratory insufficiency or failure. Underlying mechanisms of sepsis‐induced diaphragm dysfunction are mediated by inflammatory cytokines, oxidative stress, muscle atrophy, and mitochondria dysfunction, among others …”

“…Because Ca 2+ signaling is essential for muscle function, another mechanism for diaphragm dysfunction during sepsis may involve Ca 2+ handling. Impairment of diaphragm contractility during sepsis has been widely studied . One of the underlying mechanisms involves reduced expression of the ryanodine receptor (RyR), a Ca 2+ transporter on the SR that is responsible for release of Ca 2+ during contraction .…”

“…Impairment of diaphragm contractility during sepsis has been widely studied. [3][4][5][6][7] One of the underlying mechanisms involves reduced expression of the ryanodine receptor (RyR), 3 a Ca 21 transporter on the SR that is responsible for release of Ca 21 during contraction. 10 Sepsis can also cause impairment of diaphragm relaxation 11,12 ; however, direct investigation of the underlying mechanism has not yet been undertaken.…”

Myopathic characteristics in septic mechanically ventilated patients

“…2b). The expression of both DHPRa1s and RyR1 has been reported to be reduced in the diaphragm of rats 24 h after induction of intra-peritoneal sepsis [24]. Furthermore, intra-cellular interleukin (IL)-1a .…”