IP3-dependent Ca2+ release in permeabilized hepatocytes of endotoxemic and septic rats

Inositol trisphosphate-dependent Ca2+ release was measured in saponin-permeabilized hepatocytes isolated from acutely (2 mg/100 g body wt iv) or chronically (0.1 mg X 100 g body wt-1 X 24 h-1 for 30 h) endotoxin-treated (ET, Escherichia coli) rats or from animals rendered septic by cecal ligation and puncture. A decrease of this parameter was observed in acutely ET-treated rats (52%, P less than 0.01) and after 30 h of continuous ET infusion (33%, P less than 0.01). Sepsis was associated with an elevated Ca2+ release (34%, P less than 0.01) as compared with the sham-operated animals. We conclude that during endotoxicosis and sepsis alterations of intracellular Ca homeostasis take place, reaching sites beyond the level of the plasma membrane. Such alterations could account in part for metabolic and functional changes associated with these pathologic states. In addition, ET treatment provides the first known intervention resulting in the modulation of inositol trisphosphate-dependent Ca2+ release.