Related Experiment Videos
Skeletal muscle Ca2+ flux and catabolic response during sepsis
J Bhattacharyya1, K D Thompson, M M Sayeed
1Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Abstract:
Membrane Ca2+ flux and net protein catabolism were studied in the skeletal muscle during experimental sepsis. Sterilized rat fecal pellets with (septic) or without (sterile) gram-negative bacteria, Escherichia coli [10(2) colony-forming units (cfu)] and Bacteroides fragilis (2 x 10(3) cfu), were implanted into the abdomens of male Sprague-Dawley rats (110-120 g). Septic and sterile rats were febrile and hyperlactacidemic on day 1 postimplantation. These responses subsided by day 2 in sterile but not septic rats. Initial Ca2+ flux, estimated from measurements of 45Ca uptake by soleus muscles in vitro, was elevated on day 1 in both sterile and septic rats and on day 2 and 3 in septic rats only. The septic rat soleus muscle showed a significantly increased net protein catabolic response (measured as tyrosine release by soleus muscle, in vitro) over that found in muscles of sterile rats on day 1-3 postimplantation. The increase in Ca2+ flux in septic (day 1-3 postimplantation) and sterile (day 1 only) rats was abolished when the rats were treated with the calcium channel blocker diltiazem. In unoperated control rat soleus muscles the Ca2+ ionophore, ionomycin, concomitantly caused an increase in Ca2+ flux and net protein catabolism. Overall, the present study suggested that altered cellular Ca2+ regulation plays a role in the net protein catabolic response in the skeletal muscle during sepsis.
Insights
Sepsis increases calcium (Ca2+) flux and protein breakdown in rat skeletal muscle. Blocking calcium channels with diltiazem reduced these sepsis-induced effects, suggesting Ca2+ regulation is key to muscle catabolism during sepsis.
Area of Science:
- Physiology
- Biochemistry
- Pathology
Background:
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
- Skeletal muscle dysfunction and protein catabolism are common complications of sepsis.
- The role of cellular calcium (Ca2+) regulation in sepsis-induced muscle catabolism requires further elucidation.
Purpose of the Study:
- To investigate the relationship between membrane Ca2+ flux and net protein catabolism in skeletal muscle during experimental sepsis.
- To determine the impact of sepsis on Ca2+ handling and protein breakdown in rat soleus muscles.
- To explore the potential therapeutic role of calcium channel blockers in mitigating sepsis-induced muscle wasting.
Main Methods:
- Experimental sepsis was induced in male Sprague-Dawley rats by abdominal implantation of fecal pellets containing gram-negative bacteria.
- Calcium-45 (45Ca) uptake was measured in vitro to estimate Ca2+ flux in soleus muscles.
- Net protein catabolism was assessed by measuring tyrosine release from soleus muscles in vitro.
- The effects of the calcium channel blocker diltiazem and the Ca2+ ionophore ionomycin were evaluated.
Main Results:
- Septic rats exhibited elevated Ca2+ flux and significantly increased net protein catabolism in soleus muscles from day 1 to day 3 postimplantation.
- While sterile rats showed transiently increased Ca2+ flux on day 1, septic rats displayed sustained elevation.
- Diltiazem treatment abolished the sepsis-induced increase in Ca2+ flux, and ionomycin administration increased both Ca2+ flux and protein catabolism in control muscles.
Conclusions:
- Altered cellular Ca2+ regulation is implicated in the net protein catabolic response observed in skeletal muscle during experimental sepsis.
- Modulating Ca2+ flux may represent a therapeutic strategy to prevent or reduce muscle wasting in septic patients.
- These findings highlight the critical role of calcium homeostasis in maintaining skeletal muscle integrity during severe infections.