MEMBRANE-METABOLIC COUPLING AND ION HOMEOSTASIS IN ANOXIA-TOLERANT AND ANOXIA-INTOLERANT HEPATOCYTES

The relationship between membrane function and energy metabolism was s tudied in rainbow trout hepatocytes, an anoxia-intolerant cell system, and compared with the situation in hepatocytes from the goldfish, a t ypical anoxia-tolerant species. In trout hepatocytes, under normoxia a nd under chemical anoxia, inhibition of ATP consumption by the Na+ pum p induced a decrease in ATP production of the same magnitude. In respo nse to chemical anoxia, total ATP production was reduced to 15% and Na + pump activity to 22% of the control rate under normoxia. Measurement of the cellular ATP content under these conditions revealed that, des pite the reduction in Na+ pump activity, the cells became rapidly depl eted of ATP, with the time course of this process resembling that obse rved in the anoxic rat hepatocyte. This is in contrast to the response s of goldfish hepatocytes, where, during chemical anoxia, 1) inhibitio n of the Na+ pump did not lead to a corresponding reduction in ATP pro duction and 2) ATP levels, after a transient decrease, stabilized at a new steady state. To investigate the consequences of chemical anoxia on ion homeostasis, efflux and uptake rates of K+ were determined simu ltaneously. In the trout cells, chemical anoxia led to a decoupling of influx and efflux rates, the latter exceeding the former three- to ei ghtfold. In contrast, goldfish hepatocytes were able to preserve ion h omeostasis by a concerted decrease in Rb+ uptake and K+ efflux, so tha t the net flux of K+ was always close to zero. In neither species did chemical anoxia induce a change in pump density. Other potential contr ol mechanisms are briefly discussed.