Subacinar distribution of hepatocyte membrane potential response to stimulation of gluconeogenesis

Isolated rat livers were perfused and the membrane potentials of matched periportal and pericentral hepatocytes were determined using glass microelectrodes. O2 uptake and gluconeogenesis were increased by both phenylephrine and glucagon and the extent of the increase was not affected by the direction of perfusion. With no exogenous substrate, hepatocyte membrane potentials were approximately -27 mV. No gradients were found. Substrate produced hyperpolarization in all hepatocytes, with a small but significant gradient produced. Phenylephrine-induced hyperpolarization was higher in periportal than in pericentral hepatocytes during anterograde perfusion, but reversed during retrograde perfusion. Similar effects on membrane potential were produced by phorbol myristate acetate (PMA). Glucagon hyperpolarized homogeneously during both anterograde and retrograde perfusion with no gradients across the acinus. Octanol addition during glucagon stimulation, however, resulted in heterogeneity similar to phenylephrine or PMA. Thus when hepatocytes are stimulated by substrate or hormones, the degree of hepatocyte membrane potential heterogeneity across the acinus is highly dependent on the nature of the stimulus. We propose that the differential hormone effects on hepatocyte membrane potential may be mediated at least in part by differential modulation of cell to cell communication via gap junctions.