Synaptic activation of presynaptic glutamate transporter currents in nerve terminals

J Neurosci. 2003 Jun 15;23(12):4831-41. doi: 10.1523/JNEUROSCI.23-12-04831.2003.

Abstract

Glutamate uptake by high-affinity transporters is responsible for limiting the activation of postsynaptic receptors and maintaining low levels of ambient glutamate. The reuptake process generates membrane currents, which can be activated by synaptically released glutamate in glial cells and some postsynaptic neurons. However, less is known about presynaptic transporter currents because the small size of synaptic boutons precludes direct recordings. Here, we have recorded from two giant nerve terminals: bipolar cell synaptic terminals in goldfish retina and the calyx of Held in rat auditory brainstem. Exocytosis was evoked by brief depolarizations and measured as an increase in membrane capacitance. In isolated bipolar cell terminals, exocytosis was associated with an anion (NO3- or Cl-) current. The current peaked 2.8 msec after the start of the depolarization and decayed with a mean time constant of 8.5 msec. It was inhibited by the nontransportable glutamate transporter antagonist sc-threo-beta-benzyloxyaspartate (TBOA) but was insensitive to the GLT1/EAAT2 subtype-selective antagonist dihydrokainate and was affected by extracellular pH buffering. A TBOA-sensitive anion current was also evoked by application of exogenous glutamate to bipolar cell terminals. The large single-channel conductance, derived from noise analysis, and previous immunolocalization studies suggest that synaptically released glutamate activates EAAT5-type transporters in bipolar cell terminals. In contrast, neither exocytosis nor exogenous glutamate evoked a transporter current in the calyx of Held. Glutamate transporter currents with rapid kinetics are therefore identified and characterized in bipolar cell terminals, providing a valuable system for investigating the function and modulation of presynaptic glutamate transporters.

Publication types

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

MeSH terms

  • Amino Acid Transport System X-AG / metabolism*
  • Amino Acid Transport Systems*
  • Animals
  • Aspartic Acid / pharmacology
  • Auditory Pathways / physiology
  • Brain Stem / cytology
  • Brain Stem / physiology
  • Calcium Channel Blockers / pharmacology
  • Carrier Proteins / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Transporter 5
  • Exocytosis / physiology
  • Glutamic Acid / pharmacology
  • Goldfish
  • In Vitro Techniques
  • Patch-Clamp Techniques
  • Photoreceptor Cells*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / cytology
  • Retina / drug effects
  • Retina / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Amino Acid Transport System X-AG
  • Amino Acid Transport Systems
  • Calcium Channel Blockers
  • Carrier Proteins
  • Excitatory Amino Acid Antagonists
  • Excitatory Amino Acid Transporter 5
  • Slc1a7 protein, rat
  • benzyloxyaspartate
  • Aspartic Acid
  • Glutamic Acid