G-protein-mediated desensitization of metabotropic glutamatergic and muscarinic responses in CA3 cells in rat hippocampus

J Physiol. 1997 Apr 15;500 ( Pt 2)(Pt 2):487-96. doi: 10.1113/jphysiol.1997.sp022035.


1. Desensitization of a metabotropic response was investigated in CA3 pyramidal neurons in hippocampal slice cultures using the patch-clamp technique. 2. 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), an agonist at metabotropic glutamate receptors (mGluRs), and metacholine (MCh), an agonist at muscarinic receptors, induced a cationic current that appears to be activated through a G-protein-independent transduction process, as previously shown. Prolonged or repetitive bath application of agonists led to rapid desensitization of the cationic current with a time constant of approximately 20 s. 3. Complete recovery from desensitization was observed within 6 min. 4. These responses mediated by mGluRs and muscarinic receptors cross-desensitized. 5. Preventing the activation of G-proteins by loading cells with GDP beta S strongly reduced or suppressed desensitization, and resulted in a sustained inward cationic current. When cells were filled with GTP gamma S to irreversibly activate G-proteins, the desensitization process was enhanced such that a first application of agonist caused a markedly reduced response. 6. These results show that a cationic current induced by metabotropic agonists in hippocampal pyramidal cells undergoes apparent desensitization and suggests that this process occurs through a G-protein-mediated inhibition of the underlying membrane conductance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cations / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Electrophysiology
  • GTP-Binding Proteins / metabolism*
  • Glutamic Acid / pharmacology
  • Hippocampus / chemistry
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Methacholine Chloride / pharmacology
  • Muscarinic Agonists / pharmacology
  • Neurons / chemistry
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology
  • Organ Culture Techniques
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / physiology*
  • Receptors, Muscarinic / physiology*
  • Sensitivity and Specificity


  • Cations
  • Muscarinic Agonists
  • Neuroprotective Agents
  • Receptors, Metabotropic Glutamate
  • Receptors, Muscarinic
  • Cycloleucine
  • Methacholine Chloride
  • 1-amino-1,3-dicarboxycyclopentane
  • Glutamic Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • GTP-Binding Proteins