Reduced DHPRα1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis.
BACKGROUND
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.
Respiratory Department and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code, 110004, People's Republic of China.
Guang-Yu
GY
Jiao
Li-Ying
LY
Hao
Chun-E
CE
Gao
Lie
L
Chen
Xue-Fei
XF
Sun
Hua-Li
HL
Yang
Ying
Y
Li
Yi-Ning
YN
Dai
D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000378:metabolism*; D018805:Sepsis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology
D020746:Calcium Channels, L-Type; D020033:Protein Isoforms; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel
DHPR; RyR; diaphragm muscle; excitation-contraction coupling; sepsis