Ablation of Ca2+ channel β3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory
Ablation of Ca2+ channel β3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory
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DOI：
10.1074/jbc.m800816200
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发表时间：
2008-05-02
影响因子：
4.8
通讯作者：
Shin, Hee-Sup
中科院分区：
文献类型：
--
作者：
Jeon, Daejong;Song, Inseon;Shin, Hee-Sup
电压依赖性Ca2+通道（VDCCs）的β亚基对VDCCs的成孔α(1)亚基的性质有显著影响，包括通道复合物的表面表达和电压依赖性动力学的修饰。在四种不同的β亚基中，β 3亚基（Ca-v β 3）在海马中大量表达。然而，Ca-v - 3在体内海马生理和功能中的作用从未被研究过。在这里，我们研究了Ca-v β 3缺陷小鼠海马依赖性学习记忆和海马CA3-CA1突触的突触可塑性。有趣的是，突变小鼠在一些海马体依赖的学习和记忆任务中表现出更高的表现。然而，电生理研究显示突变海马的Ca2+电流密度、微型兴奋性突触后电流的频率和振幅以及基础突触传递没有改变。另一方面，n -甲基-d -天冬氨酸受体（NMDAR）介导的突触电流和NMDAR依赖的长时程增强在突变体中显著增加。蛋白印迹分析显示，突变体海马中NMDAR-2B水平略有升高。我们的研究结果表明，与VDCCs调节无关，Ca-v β 3可能负调控海马中NMDAR的活性，从而负调控小鼠活动依赖性突触可塑性和认知行为。
The beta subunits of voltage-dependent Ca2+ channels (VDCCs) have marked effects on the properties of the pore-forming alpha(1) subunits of VDCCs, including surface expression of channel complexes and modification of voltage-dependent kinetics. Among the four different beta subunits, the beta 3 subunit (Ca-v beta 3) is abundantly expressed in the hippocampus. However, the role of Ca-v beta 3 in hippocampal physiology and function in vivo has never been examined. Here, we investigated Ca-v beta 3-deficient mice for hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses. Interestingly, the mutant mice exhibited enhanced performance in several hippocampus-dependent learning and memory tasks. However, electrophysiological studies revealed no alteration in the Ca2+ current density, the frequency and amplitude of miniature excitatory postsynaptic currents, and the basal synaptic transmission in the mutant hippocampus. On the other hand, however, N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents and NMDAR-dependent long term potentiation were significantly increased in the mutant. Protein blot analysis showed a slight increase in the level of NMDAR-2B in the mutant hippocampus. Our results suggest a possibility that, unrelated to VDCCs regulation, Ca-v beta 3 negatively regulates the NMDAR activity in the hippocampus and thus activity-dependent synaptic plasticity and cognitive behaviors in the mouse.