osmolality coupled to the large fraction of cardiac output that constitutes the splanchnic-hepatic circulation minimizes shifts in external osmotic pressure, aside from those arising from pathological conditions. It also seems that any osmotic imbalance arising from cell metabolism or transport would be limited to specific cells, given the heterogeneity of metabolic functions in the hepatic lobule. Considering the large degree of intercellular communication between hepatocytes, presumably by means of gap junctions, it is questionable whether such osmotic imbalances could be sustained long enough to effect changes in protein synthesis. Second, extrapolation of the authors' linear plots of protein synthesis vs. time did not intersect the origin; instead they crossed the x-axis at 6 to 7 min. This could reflect diffusion delays. However, it also suggests that activation of a secondary cellular mechanism affects protein synthesis, other than change in cell volume, which occurs rapidly in isolated rat hepatocytes (2). It will be important to consider whether changes in activity or concentration of ionic or organic mediators affect protein synthesis, in addition to changes in water volume per se.In summary, this paper presents new and exciting results showing that changes in hepatocyte hydration affect protein synthesis. This, along with other studies (31, suggests that changes in hepatocyte volume profoundly alter macromolecular synthesis and degradation. Nevertheless, a crucial question remains to be answered: is this phenomenon of importance in normal liver function and pathophysiology, or does it result from experimental conditions triggering highly conserved, vestigial adaptations by cells to survive the dilute milieu of the Precambrian environment (4)? Regardless of the answer to this question, readers and investigators must be aware that, although this problem may be new to hepatologists, these hepatologists are sailing into well-charted waters. There is a rich history to the study of the molecular organization of cells, state of cellular water and effects that changes of organization and hydration have on cellular metabolism (5-7). This field has been rather controversial; notwithstanding, one thing seems quite clear, as aptly stated by Clegg (7): "Although dimly perceived at present, it appears that living cells exhibit an organization far greater than the current teachings of cell biology reveal." REFERENCES 1. Colclasure GC, Parker JC. Cytosolic protein concentration is the primary volume signal for swelling-induced [K-C11 cotransport in dog red cells. J Gen Physiol 1992;lOO:l-10. 2. Corasanti JG, Gleeson D, Boyer JL. Effects of osmotic stresses on isolated rat hepatocytes I. Ionic mechanisms of cell volume regulation. Am J Physiol 1990;258:G290-G298. 3. Baquet A, Hue L, Meijer AJ, van Woerkom GM, Plomp PJAM. Swelling of rat hepatocytes stimulates glycogen synthesis. J Biol Chem 1990;265:955-959. 4. Schultz SG. Volume preservation: then and now. News Physiol Sci 5. Porter KR, Tucker JB. The ground substance ...
