Cellular Ca2+ Dyshomeostasis in the Liver in Endotoxic Shock
Cellular Ca2+ homeostasis is understood to be maintained by three membrane systems viz. the plasma membrane, the inner mitochondrial and the endoplasmic reticular membranes. Each of these membranes possesses distinctive Ca2+ transport processes by means of which it regulates cytosolic Ca2+ concentration.1 While Ca2+ mobilization into the cytosolic compartment subsequent to cell activation plays an important role in the elicitation of various normal cellular responses, an inappropriate elevation of intracellular Ca2+ causes cell damage. Although the precise mechanism of cell damage remains to be understood, it could result from Ca2+ induced activation of cytolytic processes2,3 and altered regulation of enzymes required for cellular metabolism and ion transport.4,5 Several studies have implicated altered cellular Ca2+ regulation in cell damage within various organ systems of animals in septic and endotoxic shock.6,7,8 In our laboratory, we have evaluated alterations in the regulation of hepatic intracellular Ca2+ in endotoxic animals. These evaluations included measurements of (1) cellular Ca2+ efflux and its modulation by norepin- ephrine, (2) Ca2+ uptake by endoplasmic reticulum, and (3) cytoplasmic exchangeable Ca2+. In addition, cytosolic free Ca2+ concentrations were measured under basal and hormone stimulated conditions.
KeywordsEndoplasmic Reticular Membrane Liver Slice Endotoxic Shock Washout Curve Pyruvate Carboxylation
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