Ion transport in hepatocytes: mechanisms and correlations to cell volume, hormone actions and metabolism.

Intracellular ion homeostasis in liver cell is accomplished through the concerted action of ion pumps, carriers and channels. Description of these elements includes the Na+/K+-ATPase, Na+/H+- and Cl-/ HCO3(-)-exchange and Na+-HCO-3(-)- and Na(+)-K(+)-2 Cl(-)-cotransport as well as K+-, Cl(-)-, Na+ and nonselective cation channels. A short section is devoted to regulation of intracellular Ca2+ concentration. Ion flux through these elements is regulated by hormones and during experimental alterations of cell volume. We describe the effects of hormones and agonists on ion transport (e.g. purinergic agonists, alpha- and beta-adrenergic agonists, vasopressin, glucagon and insulin) and we emphasize the fact that altered ion transport rates may lead to cell swelling or cell shrinkage. Osmotically induced cell swelling or cell shrinkage triggers volume regulatory responses: recovery from cell swelling is accomplished by release of K+ and Cl- through ion channels whereas volume gain following osmotic shrinkage involves uptake of Na+, K+ and Cl- by channels, carriers and the Na+/K+-pump. Osmotic cell volume changes are associated with a broad spectrum of altered cell functions that includes changes of bile flow and bile acid transport, modulation of cytoplasmic and endosomal pH, metabolism of carbohydrate, protein and lipids, transcription and translation and alteration of cytoskeleton components (cf. Häussinger & Schliess; J. Hepatology 1995; 22: 94-100). In conclusion, we stress the concept that transduction of a hormonal signal primarily involves alteration of membrane ion transport followed by a change in cell volume. This change in cell volume appears to assist in executing a hormonal stimulus on cell function.