Inhibition of hippocampal synaptic transmission by impairment of Ral function

Neuroreport. 2005 Nov 7;16(16):1805-8. doi: 10.1097/01.wnr.0000186594.87328.c8.

Abstract

Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ras, R-Ras, Rap) both inhibited autaptic responses. In a proportion of the neurons (25%, TcdA-10463; 54%, TcsL-1522), the inhibition was associated with a shift from activity-dependent depression to facilitation, indicating that the synaptic release probability was reduced. Overexpression of a dominant negative Ral mutant, Ral A28N, caused a strong inhibition of autaptic responses, which was associated with a shift to facilitation in a majority (80%) of the neurons. These results indicate that Ral, along with at least one other non-Rab GTPase, participates in presynaptic regulation in hippocampal neurons.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Animals
  • Arabidopsis Proteins / pharmacology
  • Asparagine / genetics
  • Bacterial Toxins / pharmacology
  • Blotting, Western / methods
  • Carbon Isotopes / pharmacology
  • Cells, Cultured
  • Drug Interactions
  • Electric Stimulation / methods
  • Enterotoxins / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Glucose / metabolism
  • Hippocampus / cytology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mutation / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Rats
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Toxins, Biological / pharmacology
  • Transfection / methods
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
  • gamma-Aminobutyric Acid / pharmacology
  • ral GTP-Binding Proteins / physiology*

Substances

  • Arabidopsis Proteins
  • Bacterial Toxins
  • Carbon Isotopes
  • Enterotoxins
  • Excitatory Amino Acid Agonists
  • TSCL protein, Arabidopsis
  • Toxins, Biological
  • tcdA protein, Clostridium difficile
  • gamma-Aminobutyric Acid
  • Asparagine
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • ral GTP-Binding Proteins
  • Glucose
  • Alanine