RESUMEN
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.
Asunto(s)
Potenciales de Acción/fisiología , Hipocampo/metabolismo , Células Piramidales/metabolismo , ras-GRF1/deficiencia , Potenciales de Acción/efectos de los fármacos , Animales , Estimulación Eléctrica , Antagonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Predisposición Genética a la Enfermedad/genética , Glutamato Descarboxilasa/metabolismo , Hipocampo/citología , Hipocampo/efectos de los fármacos , Isoenzimas/metabolismo , Masculino , Ratones , Ratones Noqueados , Red Nerviosa/citología , Red Nerviosa/efectos de los fármacos , Red Nerviosa/metabolismo , Técnicas de Placa-Clamp , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Convulsiones/inducido químicamente , Convulsiones/genética , Convulsiones/metabolismo , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Sinaptofisina/metabolismo , Tetrodotoxina/farmacología , ras-GRF1/genéticaRESUMEN
The introduction of columnar defects in (K,Ba )Bi O3 single crystals shifts both the irreversibility and thermodynamic transition lines, respectively, deduced from ac susceptibility (and/or transport) and specific heat measurements, upwards. This shift can be attributed to the defect-induced decrease of the difference (Delta F) between the free energies in the superconducting and the normal states, assuming that the position of the superconducting transition is given by the condition absolute value Delta F approximately k(B )T/xi(3 ). This criterion also perfectly reproduces the influence of the angle between the tracks and the external field. This result suggests that no vortex liquid phase exists in this system.