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 IP3 receptors in regenerating liver following 70% hepatectomy, and to evaluate the hepatic Ca2+ distribution and mobilization during this process. Specific [3H]ryanodine and [3H]IP3 binding 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 of 14C amino acids into proteins and of 32P into phospholipids was done in subcellular fractions. Ryanodine receptor Kd presented a dramatic increase after 12 h of surgery and remained high up to 2 days of treatment. IP3 receptor Bmax showed 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.
Díaz-Muñoz
M
M
Departamento de Biofísica, Universidad Nacional Autonoma de México, D.F. Mexico.
Cañedo-Merino
R
R
Gutiérrez-Salinas
J
J
Hernández-Muñoz
R
R
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D006498:Hepatectomy; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium