title: Volume-dependent glutamate permeation depends on transmembrane ionic strength and extracellular Cl-.
abstract: Many mammalian cells regulate their volume by the osmotic movement of water directed by anion and cation flux. Ubiquitous volume-dependent anion currents permit cells to recover volume after swelling in response to a hypotonic environment. This study addressed competition between glutamate (Glu) and Cl(-) permeation in volume-activated anion currents in order to provide insight into the ionic requirements for volume regulation, volume-dependent anion channel activity and to the architecture of the channel pore. The effect of changing the intracellular molar fraction (MF) of Glu and Cl(-) on conductance and relative anion permeability was evaluated as a function of the extracellular permeant anion and/or the ionic strength. Relative permeability of Glu to Cl(-) was determined by measuring reversal potentials under defined ionic conditions. Under conditions with high (150 m M) or low (50 m M) ionic strength solutions on both sides of the membrane, Cl(-) was always more permeable than Glu. When a transmembrane ionic strength gradient (150 m M extracellular: 50 m M intracellular) was set to drive water into the cell, and in the presence of extracellular Cl(-), Glu became up to 16-fold more permeable than Cl(-). Replacement of extracellular Cl(-) with Glu abolished this effect. These results indicate that it is possible for Glu to move into the extracellular environment during volume-regulatory events and they support the emerging role of glutamate as a modulator of anion channel activity.
authors.affiliation: Dept. of Pharmacology and Physiology, College of Medicine, Drexel University, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Hoffman
authors.forename: S S
authors.initials: SS
authors.lastname: Garber
mesh_terms: D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D002713:Chlorine / Q000378:metabolism*; D005110:Extracellular Space / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D007477:Ions; D007668:Kidney / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D007473:Ion Channels; D007477:Ions; D018698:Glutamic Acid; D002713:Chlorine