Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability
Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability
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DOI：
10.1006/mcne.2001.1050
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发表时间：
2001-12-01
影响因子：
3.5
通讯作者：
Zippel, R
中科院分区：
文献类型：
--
作者：
Tonini, R;Franceschetti, S;Zippel, R
Ras-GRF1 是 Ras 蛋白的神经元特异性鸟嘌呤核苷酸交换因子。缺乏 Ras-GRF1 (-/-) 的小鼠杏仁核依赖性长期突触可塑性严重受损，并且杏仁核和海马突触均表现出较高的基础突触活性 (Brambilla 等人，1997)。在本研究中，我们研究了 Ras-GRF1 缺失对海马神经元兴奋性的影响。原代培养的神经元和成年海马切片的电生理分析表明 Ras-GRF1-/- 小鼠表现出神经元过度兴奋。 Ras-GRF1-/-海马神经元表现出自发活动增加和静息膜电位去极化，以及响应注入电流的更高放电率。 Ras-GRF1-/- 神经元内在兴奋性的变化可能会导致这些现象，表明 Ras-GRF1 缺陷可能会改变离子电导之间的平衡。此外，我们发现缺乏 Ras-GRF1 的小鼠在急性服用惊厥药物后表现出更高的癫痫易感性。总而言之，这些结果证明了 Ras-GRF1 在神经元兴奋性中的作用。
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.