Purinergic receptors mediate two distinct glutamate release pathways in hippocampal astrocytes
Purinergic receptors mediate two distinct glutamate release pathways in hippocampal astrocytes
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DOI：
10.1074/jbc.m510679200
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发表时间：
2006-02-17
影响因子：
4.8
通讯作者：
Carmignoto, G
中科院分区：
文献类型：
--
作者：
Fellin, T;Pozzan, T;Carmignoto, G
嘌呤能P2 X（7）受体（P2 X（7）R）可介导培养的星形胶质细胞释放谷氨酸。采用膜片钳技术，我们研究了P2 X（7）Rs是否在海马星形胶质细胞中具有相同的作用。我们发现，2-和3-O-（4-苯甲酰基苯甲酰基）ATP（BzATP），一种有效的，但非选择性的P2 X（7）R激动剂，触发两种不同的谷氨酸介导的反应，在CA 1锥体神经元;他们是短暂的内向电流，具有动力学和药理学特性的先前描述的慢内向电流（SIC）由于钙依赖性谷氨酸释放从星形胶质细胞，和持续的紧张性电流。尽管SICs不受P2 X（7）Rs拮抗剂的影响，但紧张性电流被抑制，在低细胞外Ca 2+中被放大，并且对谷氨酸转运体和半通道抑制剂不敏感。BzATP在星形胶质细胞中触发了一个大的去极化，该去极化被P2 X（7）R拮抗剂抑制，并在低Ca 2+中放大。在低钙BzATP也诱导荧光黄摄取到星形胶质细胞和CA 3神经元的亚群。我们的研究结果表明，除了P2 X（7）R以外的嘌呤能受体介导谷氨酸释放，引起SICs，而具有类似于P2 X（7）R特征的受体的激活介导持续的谷氨酸流出，在CA 1神经元中产生强直电流。这种在非生理条件下增强的持续谷氨酸流出可能在脑中具有重要的病理作用。
The purinergic P2X(7) receptor (P2X(7)R) can mediate glutamate release from cultured astrocytes. Using patch clamp recordings, we investigated whether P2X(7)Rs have the same action in hippocampal astrocytes in situ. We found that 2- and 3-O-(4-benzoylbenzoyl) ATP (BzATP), a potent, although unselective P2X(7)R agonist, triggers two different glutamate-mediated responses in CA1 pyramidal neurons; they are transient inward currents, which have the kinetic and pharmacological properties of previously described slow inward currents (SICs) due to Ca2+-dependent glutamate release from astrocytes, and a sustained tonic current. Although SICs were unaffected by P2X(7)Rs antagonists, the tonic current was inhibited, was amplified in low extracellular Ca2+, and was insensitive to glutamate transporter and hemichannel inhibitors. BzATP triggered in astrocytes a large depolarization that was inhibited by P2X(7)R antagonists and amplified in low Ca2+. In low Ca2+ BzATP also induced lucifer yellow uptake into a subpopulation of astrocytes and CA3 neurons. Our results demonstrate that purinergic receptors other than the P2X(7)R mediate glutamate release that evokes SICs, whereas activation of a receptor that has features similar to the P2X(7)R, mediates a sustained glutamate efflux that generates a tonic current in CA1 neurons. This sustained glutamate efflux, which is potentiated under non-physiological conditions, may have important pathological actions in the brain.