title: Regulation of transmembrane electrical potential gradient in rat hepatocytes in situ.
abstract: The transmembrane electrical potential gradient (Em) has been measured in hepatocytes from intact anesthetized rats using conventional intracellular microelectrodes under a variety of conditions. Em measurements in control animals were normally distributed around a mean of -35.5 +/- 4.6 mV (SD) with a coefficient of variation (CV) of 13.1% and a range of -26 to -54 mV. In individual livers, however, measurements of Em at a given point in time exhibited little cell-to-cell variation (cv of 4.5%). The Em was noted to fluctuate spontaneously over time and to change consistently in response to a variety of physiological stimuli including fasting (depolarization to -28.5 +/- 3.8 mV) and infusion of glucagon in physiological amounts (hyperpolarization to -45.0 +/- 1.8 mV). Hepatocyte Em abruptly depolarized (2-5 mV) after an intravenous bolus of taurocholate (3 mumol) or alanine (45 mumol), suggesting that both solutes exhibit electrogenic uptake. The Em returned to or below preinfusion values within 5 min. Continued infusion of alanine (10.8 mumol/min), but not taurocholate (810 nmol/min), caused a sustained and unexpected hyperpolarization of Em of 8.2 +/- 3.1 mV that lasted at least 60 min. In separate studies, alanine administration did not alter the biliary excretion of a taurocholate load. Taken together, these observations demonstrate that rat hepatocytes in situ are tightly coupled electrically and that physiological stimuli, including fasting, glucagon, and sodium-coupled solute uptake can change Em considerably over time. The late hyperpolarization of Em caused by alanine appears to offset the rise in intracellular Na+ associated with alanine uptake and preserve the Na+ electrochemical gradient such that Na+-coupled taurocholate transport is maintained.
mesh_terms: D000409:Alanine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D005215:Fasting; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D013656:Taurocholic Acid; D005934:Glucagon; D000409:Alanine