Modulation of BK channels contributes to activity-dependent increase of excitability through MTORC1 activity in CA1 pyramidal cells of mouse hippocampus.
Modulation of BK channels contributes to activity-dependent increase of excitability through MTORC1 activity in CA1 pyramidal cells of mouse hippocampus.
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DOI：
10.3389/fncel.2014.00451
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发表时间：
2014
影响因子：
5.3
通讯作者：
Schrader LA
中科院分区：
文献类型：
--
作者：
Springer SJ;Burkett BJ;Schrader LA
记忆获得和突触可塑性伴随着CA 1锥体神经元内在兴奋性的变化。兴奋性的这些活动依赖性变化是由内在电流的调制介导的，内在电流改变了细胞对突触输入的反应性。后超极化（AHP），神经元兴奋性的调节的一个主要贡献者，是减少在动物中获得了几种类型的视皮层依赖的记忆任务，并通过高频刺激突触增强。BK通道的基础上的快速层次分析法，并有助于尖峰复极，这层次分析法是减少动物成功收购跟踪眨眼条件。这表明BK通道功能是活性依赖性的，但机制尚不清楚。在这项研究中，我们发现用paxilline（10 μM）阻断BK通道可降低IAHP振幅，增加+100 pA去极化时的峰电位半宽和瞬时频率。此外，θ脉冲刺激（TBS）诱导的长时程增强（LTP）降低了BK通道对IAHP、锋电位复极化和瞬时频率的贡献。这一结果表明，BK通道活性降低突触增强。有趣的是，在突触增强后用雷帕霉素（400 nM）阻断哺乳动物雷帕霉素靶蛋白（MTORC 1）恢复了BK通道功能，表明蛋白质翻译在突触增强后降低突触后BK通道活性的信号传导事件中的作用。
Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent changes in excitability are mediated by modulation of intrinsic currents which alters the responsiveness of the cell to synaptic inputs. The afterhyperpolarization (AHP), a major contributor to the regulation of neuronal excitability, is reduced in animals that have acquired several types of hippocampus-dependent memory tasks and also following synaptic potentiation by high frequency stimulation. BK channels underlie the fast AHP and contribute to spike repolarization, and this AHP is reduced in animals that successfully acquired trace-eyeblink conditioning. This suggests that BK channel function is activity-dependent, but the mechanisms are unknown. In this study, we found that blockade of BK channels with paxilline (10 μM) decreased IAHP amplitude and increased spike half-width and instantaneous frequency in response to a +100 pA depolarization. In addition, induction of long term potentiation (LTP) by theta burst stimulation (TBS) in CA1 pyramidal neurons reduced BK channel’s contribution to IAHP, spike repolarization, and instantaneous frequency. This result indicates that BK channel activity is decreased following synaptic potentiation. Interestingly, blockade of mammalian target of rapamycin (MTORC1) with rapamycin (400 nM) following synaptic potentiation restored BK channel function, suggesting a role for protein translation in signaling events which decreased postsynaptic BK channel activity following synaptic potentiation.
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影响因子：
2
作者：
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通讯作者：
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DOI：
10.1073/pnas.0807708106
发表时间：
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10.1073/pnas.0805855105
发表时间：
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影响因子：
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作者：
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