Modifications of Intracellular Calcium Release Channels and Calcium Mobilization Following 70% Hepatectomy

The aim of this study was to investigate the properties of ryanodine and IP3receptors in regenerating liver following 70% hepatectomy, and to evaluate the hepatic Ca2+distribution and mobilization during this process. Specific [3H]ryanodine and [3H]IP3binding to hepatic smooth endoplasmic reticulum membranes, as well as subcellular Ca2+determination by atomic absorption flame photometry and Ca2+mobilization by INDO-1 AM spectrofluorescence in hepatocytes, was performed in regenerating livers after surgical 70% hepatectomy. Incorporation of14C amino acids into proteins and of32P into phospholipids was done in subcellular fractions. Ryanodine receptorKdpresented a dramatic increase after 12 h of surgery and remained high up to 2 days of treatment. IP3receptorBmaxshowed a significant augmentation starting at 6 h after hepatectomy and returning to normal values after 1 week. Cytosolic total calcium content decreased from 12 h until 4 days after hepatectomy whereas the microsomal and mitochondrial total calcium increased at 1 and 2–4 days of liver regeneration, which coincided with the differential turnover of proteins and phospholipids in these fractions. ATP-induced Ca2+transients in hepatocytes of 24-h-hepatectomized rats confirmed the altered sensitivity of the ryanodine receptor toward its ligand, since 10 times more ryanodine was necessary to alter the ATP-induced Ca2+transient. The data support the notion that the calcium release channels are targets of mechanisms of metabolic control during the proliferative response following 70% hepatectomy and might be part of the modified intracellular Ca2+dynamics during liver regeneration.