Associations between transports of alanine and cations across cell membrane in rat hepatocytes.
Alanine transport across the liver cell membrane is a regulated key process in the amino acid metabolism of the body. The majority of alanine influx in hepatocytes is Na+ dependent and is stimulated by intracellular negativity. The molar ratio between cotransported Na+ and alanine is 1:1. Alanine efflux is stimulated by intracellular Na+, whereas the role of the membrane potential is unclear. The transmembrane Na+ electrochemical gradient seems to be the exclusive driving force for cellular alanine accumulation. At a physiological Na+ gradient, intracellular alanine can exceed the extracellular concentration about 20-fold, but metabolism will exert a conspicuous sink effect. Na+-coupled uptake of alanine appears to be a challenge that triggers a sequence of regulatory events: increased cellular Na+ leads to an increase in active Na+-K+-pumping and thus in K+ influx; influx of alanine and cations tends to increase the cellular content of osmotically active substances implying a tendency to water uptake; cell swelling, even when modest, induces an increase in the permeability of a conductive pathway for K+ leading to net efflux of K+ (with accompanying anions) and cellular hyperpolarization. Net efflux of K+ prevents excessive cell volume increase during amino acid accumulation, whereas hyperpolarization tends to support the driving force for alanine influx (and anion efflux). The pathway for K+ efflux needs further characterization, but it may involve single-file diffusion with Ca2+ as an activator. This model suggests that cell volume regulatory processes mainly serve to compensate for changes in intracellular content of ions and metabolites during activation of specialized cellular processes.
D000409:Alanine / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002414:Cations, Monovalent; D002462:Cell Membrane / Q000378:metabolism; D004563:Electrochemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*
D002414:Cations, Monovalent; D012964:Sodium; D000409:Alanine; D011188:Potassium