Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability.

Abstract

Ras-GRF1 is a neuron-specific guanine nucleotide exchange factor for Ras proteins. Mice lacking Ras-GRF1 (-/-) are severely impaired in amygdala-dependent long-term synaptic plasticity and show higher basal synaptic activity at both amygdala and hippocampal synapses (Brambilla et al., 1997). In the present study we investigated the effects of Ras-GRF1 deletion on hippocampal neuronal excitability. Electrophysiological analysis of both primary cultured neurons and adult hippocampal slices indicated that Ras-GRF1-/- mice displayed neuronal hyperexcitability. Ras-GRF1-/- hippocampal neurons showed increased spontaneous activity and depolarized resting membrane potential, together with a higher firing rate in response to injected current. Changes in the intrinsic excitability of Ras-GRF1-/- neurons can entail these phenomena, suggesting that Ras-GRF1 deficiency might alter the balance between ionic conductances. In addition, we showed that mice lacking Ras-GRF1 displayed a higher seizure susceptibility following acute administration of convulsant drugs. Taken together, these results demonstrated a role for Ras-GRF1 in neuronal excitability.

• Authors: R Tonini, S Franceschetti, D Parolaro, M Sala, E Mancinelli, S Tininini, R Brusetti, G Sancini, R Brambilla, E Martegani, E Sturani, R Zippel
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 18 Issue 6 Pg. 691-701 (Dec 2001) ISSN: 1044-7431 [Print] United States
• PMID: 11749043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Isoenzymes
• Synaptophysin
• ras-GRF1
• Tetrodotoxin
• Glutamate Decarboxylase
• glutamate decarboxylase 1

Topics

• Action Potentials (drug effects, physiology)
• Animals
• Electric Stimulation
• Excitatory Amino Acid Antagonists (pharmacology)
• Excitatory Postsynaptic Potentials (drug effects, physiology)
• Female
• Genetic Predisposition to Disease (genetics)
• Glutamate Decarboxylase (metabolism)
• Hippocampus (cytology, drug effects, metabolism)
• Isoenzymes (metabolism)
• Male
• Mice
• Mice, Knockout
• Nerve Net (cytology, drug effects, metabolism)
• Patch-Clamp Techniques
• Pyramidal Cells (cytology, drug effects, metabolism)
• Seizures (chemically induced, genetics, metabolism)
• Synaptic Transmission (drug effects, physiology)
• Synaptophysin (metabolism)
• Tetrodotoxin (pharmacology)
• ras-GRF1 (deficiency, genetics)