MODIFICATIONS OF INTRACELLULAR CALCIUM-RELEASE CHANNELS AND CALCIUM MOBILIZATION FOLLOWING 70-PERCENT HEPATECTOMY

The aim of this study was to investigate the properties of ryanodine a nd IP3 receptors in regenerating liver following 70% hepatectomy, and to evaluate the hepatic Ca2+ distribution and mobilization during this process, Specific [H-3]ryanodine and [H-3]Ips binding to hepatic smoo th endoplasmic reticulum membranes, as well as subcellular Ca2+ determ ination by atomic absorption flame photometry and Ca2+ mobilization by INDO-1 AM spectrofluorescence in hepatocytes, was performed in regene rating livers after surgical 70% hepatectomy. Incorporation of C-14 am ino acids into proteins and of P-32 into phospholipids was done in sub cellular fractions, Ryanodine receptor K-d presented a dramatic increa se after 12 h of surgery and remained high up to 2 days of treatment, IP3 receptor B-max showed a significant augmentation starting at 6 h a fter hepatectomy and returning to normal values after 1 week, Cytosoli c total calcium content decreased from 12 h until 4 days after hepatec tomy whereas the microsomal and mitochondrial total calcium increased at 1 and 2-4 days of liver regeneration, which coincided with the diff erential turnover of proteins and phospholipids in these fractions, AT P-induced Ca2+ transients in hepatocytes of 24-h-hepatectomized rats c onfirmed the altered sensitivity of the ryanodine receptor toward its ligand, since 10 times more ryanodine was necessary to alter the ATP-i nduced Ca2+ transient, The data support the notion that the calcium re lease channels are targets of mechanisms of metabolic control during t he proliferative response following 70% hepatectomy and might be part of the modified intracellular Ca2+ dynamics during liver regeneration, (C) 1998 Academic Press.