Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate receptors

Nature. 2006 Oct 12;443(7112):705-8. doi: 10.1038/nature05123. Epub 2006 Oct 1.

Abstract

Feedback inhibition at reciprocal synapses between A17 amacrine cells and rod bipolar cells (RBCs) shapes light-evoked responses in the retina. Glutamate-mediated excitation of A17 cells elicits GABA (gamma-aminobutyric acid)-mediated inhibitory feedback onto RBCs, but the mechanisms that underlie GABA release from the dendrites of A17 cells are unknown. If, as observed at all other synapses studied, voltage-gated calcium channels (VGCCs) couple membrane depolarization to neurotransmitter release, feedforward excitatory postsynaptic potentials could spread through A17 dendrites to elicit 'surround' feedback inhibitory transmission at neighbouring synapses. Here we show, however, that GABA release from A17 cells in the rat retina does not depend on VGCCs or membrane depolarization. Instead, calcium-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs), activated by glutamate released from RBCs, provide the calcium influx necessary to trigger GABA release from A17 cells. The AMPAR-mediated calcium signal is amplified by calcium-induced calcium release (CICR) from intracellular calcium stores. These results describe a fast synapse that operates independently of VGCCs and membrane depolarization and reveal a previously unknown form of feedback inhibition within a neural circuit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / cytology
  • Amacrine Cells / drug effects
  • Amacrine Cells / metabolism
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling* / drug effects
  • Glutamic Acid / metabolism
  • Kinetics
  • Membrane Potentials / drug effects
  • Neurotransmitter Agents / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Retina / cytology*
  • Retina / metabolism*
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism
  • Synapses / drug effects
  • Synapses / metabolism
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Neurotransmitter Agents
  • Receptors, AMPA
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Calcium