Synergistic release of Ca2+ from IP3-sensitive stores evoked by synaptic activation of mGluRs paired with backpropagating action potentials

Neuron. 1999 Nov;24(3):727-37. doi: 10.1016/s0896-6273(00)81125-3.

Abstract

Increases in postsynaptic [Ca2+]i can result from Ca2+ entry through ligand-gated channels or voltage-gated Ca2+ channels, or through release from intracellular stores. Most attention has focused on entry through the N-methyl-D-aspartate (NMDA) receptor in causing [Ca2+]i increases since this pathway requires both presynaptic stimulation and postsynaptic depolarization, making it a central component in models of synaptic plasticity. Here, we report that repetitive synaptic activation of metabotropic glutamate receptors (mGluRs), paired with backpropagating action potentials, causes large, wave-like increases in [Ca2+]i predominantly in restricted regions of the proximal apical dendrites and soma of hippocampal CA1 pyramidal neurons. [Ca2+]i changes of several micromolars can be reached by regenerative release caused by the synergistic effect of mGluR-generated inositol 1,4,5-trisphosphate (IP3) and spike-evoked Ca2+ entry acting on the IP3 receptor.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Drug Synergism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Inositol 1,4,5-Trisphosphate / physiology*
  • Intracellular Membranes / metabolism
  • Osmolar Concentration
  • Pyramidal Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / physiology*
  • Synapses / physiology*

Substances

  • Receptors, Metabotropic Glutamate
  • Inositol 1,4,5-Trisphosphate
  • Calcium