Alterations in intracellular Ca2+-homeostasis of skeletal muscle fibers during sepsis

Objective: To investigate changes in intracellular Ca2+ -regulation and Ca2+-sensitivityof the contractile apparatus in murine skeletal muscle fibers during sepsis. Design and Setting. Animal study in a university-based research laboratory. Subjects: Isolated muscle fibers (M. extensor digitorum longus) of septic mice. Interventions: In one group, sepsis was induced in black six mice using cecal ligation and puncture (CLP). In a second group, laparotomy (SHAM), and in a third group, general anesthesia (GA) was performed. Saponin-skinned skeletal muscle fibers were examined 2, 3, 5, and 7 days after treatment, and caffeine-induced Ca2+-release from the sarcoplasmic reticulum (SR) as well as Ca2+-sensitivity of the contractile apparatus were assessed. Measurements and Results: In the CLP group, Ca2+-release significantly decreased over 5 days and increased again after 7 days. In the SHAM group, Ca2+-release decreased at days 2 and 3, whereas no changes were observed in the GA group. Ca (2+)- sensitivity significantly increased over 5 days in the CLP group and decreased again at day 7. In the SHAM group, Ca2+-sensitivity increased at days 2 and 3, and no changes were seen in the GA group. Conclusions: In murine skeletal muscle fibers, Ca2+-release from the SR decreases during sepsis, with effects being most pronounced 2-3 days after CLP. In parallel, Ca2+-sensitivity of the contractile apparatus is increased, and all changes are reversible. Thus, these effects might be involved in skeletal muscle dysfunction during sepsis as corresponding changes are less pronounced or absent in control groups.