Group I mGluR activation causes voltage-dependent and -independent Ca2+ rises in hippocampal pyramidal cells

J Neurophysiol. 1999 Jun;81(6):2903-13. doi: 10.1152/jn.1999.81.6.2903.


Application of the metabotropic glutamate receptor (mGluR) agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) or the selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) depolarized both CA3 and CA1 pyramidal cells in guinea pig hippocampal slices. Simultaneous recordings of voltage and intracellular Ca2+ levels revealed that the depolarization was accompanied by a biphasic elevation of intracellular Ca2+ concentration ([Ca2+]i): a transient calcium rise followed by a delayed, sustained elevation. The transient [Ca2+]i rise was independent of the membrane potential and was blocked when caffeine was added to the perfusing solution. The sustained [Ca2+]i rise appeared when membrane depolarization reached threshold for voltage-gated Ca2+ influx and was suppressed by membrane hyperpolarization. The depolarization was associated with an increased input resistance and persisted when either the transient or sustained [Ca2+]i responses was blocked. mGluR-mediated voltage and [Ca2+]i responses were blocked by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) or (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG). These data suggest that in both CA3 and CA1 hippocampal cells, activation of group I mGluRs produced a biphasic accumulation of [Ca2+]i via two paths: a transient release from intracellular stores, and subsequently, by influx through voltage-gated Ca2+ channels. The concurrent mGluR-induced membrane depolarization was not caused by the [Ca2+]i rise.

Publication types

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

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Guinea Pigs
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Ion Channel Gating
  • Membrane Potentials / physiology
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / pharmacology
  • Patch-Clamp Techniques
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*


  • Calcium Channels
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Caffeine
  • Methoxyhydroxyphenylglycol
  • Calcium
  • 3,4-dihydroxyphenylglycol