12-Lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels.
12-Lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels.
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DOI：
10.1523/jneurosci.2168-09.2010
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发表时间：
2010-02-03
期刊：
影响因子：
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通讯作者：
Siegelbaum SA
中科院分区：
文献类型：
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作者：
DeCostanzo AJ;Voloshyna I;Rosen ZB;Feinmark SJ;Siegelbaum SA
虽然长时程增强（LTP）已被深入研究，但对于哪些分子介导和调节LTP仍存在分歧。这在一定程度上是由于存在由不同的刺激模式诱导的机械上不同形式的LTP，并且依赖于不同的Ca 2+来源。在这里，我们报告了一个新的作用花生四烯酸代谢酶12-脂氧合酶（12-LO）在LTP在CA 3-CA 1海马突触，这是依赖于强直刺激的模式。我们发现，12-LO活性是必需的诱导LTP响应θ-突发刺激（TBS）协议，这取决于通过NMDA受体和L-型电压门控Ca 2+通道的Ca 2+内流。相反，由100 Hz强直刺激诱导的LTP不需要12-LO，其需要通过NMDA受体而不是L型通道的Ca 2+内流。我们发现，12-LO调节LTP通过增强突触后体树突Ca 2+内流通过L型通道在theta爆发刺激，一个行动施加通过12（S）-HPETE，12-LO的下游代谢产物。这些结果有助于确定长期存在争议的信号酶在LTP中的作用。
Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP.