Following the observations of Haussinger and Lang, 6 evidence for important functional interactions between membrane transport, metabolism, and cell volume in liver has continued to accumulate. While all cells are capable of volume regulation, there is increasing evidence in liver that small changes in the set point of volume above or below starting values initiate a complex signaling cascade that involves changes in cellular kinases, protein activity, and gene expression. Moreover, volume-sensitive ATP release provides a pathway for coordinating volume-sensitive responses along the sinusoidal and bile secretory axis. The concept that hepatocyte volume serves as a signal regulating liver cell and organ function provides a conceptual framework for development of new strategies for pharmacologic modulation of liver metabolism and bile formation through effects on volume-sensitive signaling and ion channels.
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