Involvement of CDC25Mm/Ras-GRF1-Dependent Signaling in the Control of Neuronal Excitability |
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Authors: | Raffaella Tonini Silvana Franceschetti Daniela Parolaro Mariaelvina Sala Enzo Mancinelli Silvia Tininini Ronny Brusetti Giulio Sancini Riccardo Brambilla Enzo Martegani Emmapaola Sturani Renata Zippel |
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Institution: | Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, 20133 Milan, Italy. |
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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. |
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