A GABA transporter operates asymmetrically and with variable stoichiometry

Neuron. 1994 Oct;13(4):949-60. doi: 10.1016/0896-6273(94)90260-7.


Membrane currents produced by the expression of a rat GABA transporter (GAT-1) stably transfected into HEK293 cells were characterized with a whole-cell voltage clamp. Three modes of function were identified: ex-gated currents produced by extracellular GABA, in-gated currents produced by intracellular GABA, and uncoupled currents produced in the absence of GABA. The ex-gated current was not the reversal of the in-gated current; moreover, the stoichiometry between GABA and co-ions was not always fixed. Each mode of function required a different set of ions on the two sides of the membrane. We made rapid solution changes and observed an allosteric effect of Na+ that only occurred at the extracellular surface. Thus, the GAT-1 transporter does not behave like a recirculating carrier but may be described as a pore with ion gates at either end that are controlled in part by allosteric sites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Site
  • Animals
  • Base Sequence
  • Biological Transport
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Line
  • Electric Conductivity
  • GABA Plasma Membrane Transport Proteins
  • Ion Channel Gating / drug effects
  • Ion Channels / physiology
  • Membrane Potentials / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Organic Anion Transporters*
  • Rats
  • Sodium / pharmacology
  • Thermodynamics
  • Transfection
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology


  • Carrier Proteins
  • GABA Plasma Membrane Transport Proteins
  • Ion Channels
  • Membrane Proteins
  • Membrane Transport Proteins
  • Organic Anion Transporters
  • Slc6a1 protein, rat
  • gamma-Aminobutyric Acid
  • Sodium