2-Aminoethoxydiphenyl-borate (2-APB) increases excitability in pyramidal neurons.
2-Aminoethoxydiphenyl-borate (2-APB) increases excitability in pyramidal neurons.
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DOI：
10.1016/j.ceca.2008.11.003
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发表时间：
2009-03
期刊：
影响因子：
4
通讯作者：
Yeckel MF
中科院分区：
文献类型：
--
作者：
Hagenston AM;Rudnick ND;Boone CE;Yeckel MF
从三磷酸肌醇（IP 3）敏感的细胞内储存释放的钙离子（Ca 2+）可能参与新皮层和海马锥体神经元兴奋性的短暂和长期调节。IP 3受体（IP 3R）拮抗剂代表了将IP 3产生和IP 3R依赖性内部Ca 2+释放的这些后果与其他同时刺激的第二信使信号传导级联和Ca 2+来源的作用分离的重要工具。在这项研究中，我们已经描述了行动的IP 3R和存储操作的Ca ~（2+）通道拮抗剂，2-氨基乙氧基二苯基硼酸盐（2-APB），对内部Ca ~（2+）释放和质膜兴奋性在新皮层和海马锥体神经元。具体来说，我们发现足以减弱或阻断IP 3介导的内部Ca 2+释放的2-APB（100 µM）剂量也会提高锥体神经元的兴奋性。2-APB依赖性兴奋性增加在洗脱后逆转，其特征为输入电阻增加、动作电位起始延迟减少、动作电位宽度增加、后超极化（AHPs）幅度减少和后棘波后去极化（ADPs）幅度增加。从这些观察结果中，我们得出结论，2-APB有效地和可逆地增加神经元的兴奋性，可能通过抑制电压和Ca 2+依赖性钾（K+）电导。
Calcium ions (Ca2+) released from inositol trisphosphate (IP3)-sensitive intracellular stores may participate in both the transient and extended regulation of neuronal excitability in neocortical and hippocampal pyramidal neurons. IP3 receptor (IP3R) antagonists represent an important tool for dissociating these consequences of IP3 generation and IP3R-dependent internal Ca2+ release from the effects of other, concurrently stimulated second messenger signaling cascades and Ca2+ sources. In this study, we have described the actions of the IP3R and store-operated Ca2+ channel antagonist, 2-aminoethoxydiphenyl-borate (2-APB), on internal Ca2+ release and plasma membrane excitability in neocortical and hippocampal pyramidal neurons. Specifically, we found that a dose of 2-APB (100 µM) sufficient for attenuating or blocking IP3-mediated internal Ca2+ release also raised pyramidal neuron excitability. The 2-APB-dependent increase in excitability reversed upon washout and was characterized by an increase in input resistance, a decrease in the delay to action potential onset, an increase in the width of action potentials, a decrease in the magnitude of afterhyperpolarizations (AHPs), and an increase in the magnitude of post-spike afterdepolarizations (ADPs). From these observations, we conclude that 2-APB potently and reversibly increases neuronal excitability, likely via the inhibition of voltage- and Ca2+-dependent potassium (K+) conductances.
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影响因子：
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