Time-courses of hepatocellular hyperpolarization and cyclic adenosine 3',5'-monophosphate accumulation after partial hepatectomy in the rat. Effects of fasting for 48 hours and intravenous injection of glucose.

Hepatic cell membrane potentials, hepatic cyclic adenosine 3',5'-monophosphate concentrations, and blood glucose levels were measured in anesthetized rats before, and at various times after, partial hepatectomy. In fed rats, hyperpolarization became evident 1-3 h postoperatively, reached its first peak at 4 h, and was maintained for approximately 36 h. The early phase of hyperpolarization was preceded by depletion of glycogen from the liver remnant and occurred during a decline of blood glucose concentrations below the level in sham-operated rats. Preoperative exhaustion of glycogen stores by fasting for 48 h resulted in marked hyperpolarization within 15 min after partial hepatectomy. In fasted rats, an intravenous injection of glucose (10 mmol X kg-1) caused a delay in hyperpolarization when given 30 min before partial hepatectomy, or a transient normalization of the membrane potentials when given 30 min after partial hepatectomy. Liver tissue cyclic adenosine 3',5'-monophosphate concentrations in fed rats remained largely unchanged 2 h after partial hepatectomy but increased greatly at 4 h. On the other hand, in fasted rats a significant increase was seen within 30 min. Glucose administration to fasted rats depressed cyclic adenosine 3',5'-monophosphate concentrations in the liver remnant. The results suggest that intensified gluconeogenesis, partly mediated by cyclic adenosine 3',5'-monophosphate, could be the event underlying early hepatocellular hyperpolarization induced by partial hepatectomy.