Inhibition of post-synaptic Kv7/KCNQ/M channels facilitates long-term potentiation in the hippocampus.
Inhibition of post-synaptic Kv7/KCNQ/M channels facilitates long-term potentiation in the hippocampus.
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DOI：
10.1371/journal.pone.0030402
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mellor JR
中科院分区：
文献类型：
--
作者：
Petrovic MM;Nowacki J;Olivo V;Tsaneva-Atanasova K;Randall AD;Mellor JR
乙酰胆碱受体(MAChR)的激活促进了突触可塑性的诱导，增强了认知功能。在海马区，CA1锥体细胞上的M1 mAChR既抑制小电导钙激活的钾通道，又抑制电压激活的KV7钾通道。抑制KCa通道可通过突触后NMDAR(NMDAR)促进钙离子内流，从而促进长时程增强(LTP)。据报道，抑制KV7通道也有助于LTP，但其作用机制尚不清楚。在这里，我们证明了用XE-991抑制KV7通道促进了由theta Burst配对在Schaffer侧支连合突触在大鼠海马片上诱导的LTP。同样，使用动态钳位方法消除KV7通道电导也促进了LTP。用XE-991或动态钳制阻断KV7通道不能增强突触对突触刺激的NMDAR活性。相反，抑制KV7通道增加了动作电位爆发后去极化的幅度和持续时间。此外，XE-991的作用被重新引入具有动态钳位的类似KV7的电导所逆转。这些数据表明，在LTP诱导过程中，KV7通道抑制通过增强突触后动作电位爆发期间和之后的去极化来促进NMDAR的开放。因此，在LTP M1的诱导过程中，mAChRs通过两种不同的机制促进NMDAR的开放，即抑制KCa~(2+)和KV7通道。
Activation of muscarinic acetylcholine receptors (mAChR) facilitates the induction of synaptic plasticity and enhances cognitive function. In the hippocampus, M1 mAChR on CA1 pyramidal cells inhibit both small conductance Ca2+-activated KCa2 potassium channels and voltage-activated Kv7 potassium channels. Inhibition of KCa2 channels facilitates long-term potentiation (LTP) by enhancing Ca2+calcium influx through postsynaptic NMDA receptors (NMDAR). Inhibition of Kv7 channels is also reported to facilitate LTP but the mechanism of action is unclear. Here, we show that inhibition of Kv7 channels with XE-991 facilitated LTP induced by theta burst pairing at Schaffer collateral commissural synapses in rat hippocampal slices. Similarly, negating Kv7 channel conductance using dynamic clamp methodologies also facilitated LTP. Negation of Kv7 channels by XE-991 or dynamic clamp did not enhance synaptic NMDAR activation in response to theta burst synaptic stimulation. Instead, Kv7 channel inhibition increased the amplitude and duration of the after-depolarisation following a burst of action potentials. Furthermore, the effects of XE-991 were reversed by re-introducing a Kv7-like conductance with dynamic clamp. These data reveal that Kv7 channel inhibition promotes NMDAR opening during LTP induction by enhancing depolarisation during and after bursts of postsynaptic action potentials. Thus, during the induction of LTP M1 mAChRs enhance NMDAR opening by two distinct mechanisms namely inhibition of KCa2 and Kv7 channels.
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影响因子：
3.5
作者：
Fontan-Lozano, Angela;Suarez-Pereira, Irene;Manuel Carrion, Angel
通讯作者：
Manuel Carrion, Angel
影响因子：
5.3
作者：
Li, Y;Gamper, N;Shapiro, MS
通讯作者：
Shapiro, MS
影响因子：
30.8
作者：
Charlier, C;Singh, NA;Leppert, M
通讯作者：
Leppert, M
影响因子：
3.4
作者：
Brown, Jon T.;Booth, Clair A.;Randall, Andrew D.
通讯作者：
Randall, Andrew D.
影响因子：
7.3
作者：
MARRION, NV;SMART, TG;BROWN, DA
通讯作者：
BROWN, DA