An acute effect of neuregulin 1β to suppress α7-containing nicotinic acetylcholine receptors in hippocampal interneurons
An acute effect of neuregulin 1β to suppress α7-containing nicotinic acetylcholine receptors in hippocampal interneurons
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DOI：
10.1523/jneurosci.1794-06.2006
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Fischbach, Gerald D.
中科院分区：
文献类型：
--
作者：
Chang, Qing;Fischbach, Gerald D.
我们研究了神经调节蛋白（NRG）对位于海马辐射层的中间神经元中烟碱乙酰胆碱（ACh）受体的快速作用。两种类型的反应，检测到ACh短暂脉冲后的全细胞记录。一种类型是快速上升和下降（单相）电流，可被methylylycaconitine阻断。另一种是类似的快速响应，然后是更缓慢的上升和下降电流。双相反应的慢成分对甲基甘草次酸耐药。灌注或局部应用NRG 1 β可迅速降低快内向ACh电流。NRG 1 β对慢反应没有影响。ErbB酪氨酸激酶抑制剂PD 158780（4-[（3-溴苯基）氨基]-6-（甲氨基）-吡啶并[3，4-d]吡啶亚胺）可消除NRG 1 β抑制。鬼笔环肽和细胞松弛素D也能抑制NRG 1 β的作用。此外，NRG 1 β减少了表面Alexa Fluor 488 α-银环蛇毒素结合位点的数量。我们认为NRG 1 β诱导的ACh电流抑制是由于蛋白酪氨酸磷酸化引起的受体内化。值得注意的是，在毒蕈碱、离子型谷氨酸和GABA受体拮抗剂存在下诱发的快速烟碱EPSC也被NRG 1 β降低。因此，在中枢神经系统ACh受体介导的突触效应的研究中，NRG的短期和长期效应必须考虑在内。
We examined rapid effects of neuregulin (NRG) on nicotinic acetylcholine (ACh) receptors in interneurons located in the stratum radiatum of the hippocampus. Two types of response were detected by whole-cell recordings after brief pulses of ACh. One type was a rapidly rising and falling (monophasic) current that was blocked by methyllycaconitine. The other type was a similar fast response followed by a more slowly rising and falling current. The slow component of the biphasic response was resistant to methyllycaconitine. Perfusion or local application with NRG1 beta rapidly decreased fast inward ACh currents. NRG1 beta had no effect on slow responses. NRG1 beta suppression was abolished by the ErbB tyrosine kinase inhibitor PD 158780 (4-[(3-bromophenyl)amino]-6-(methylamino)-pyrido[3,4-d] pyridimine). The NRG 1 beta effect was also inhibited by phalloidin and cytochalasin D. Furthermore, NRG 1 beta decreased the number of surface Alexa Fluor 488 alpha-bungarotoxin binding sites. We believe that the NRG 1 beta-induced inhibition of ACh currents is because of receptor internalization trigged by protein tyrosine phosphorylation. Significantly, fast nicotinic EPSCs evoked in the presence of muscarinic, ionotropic glutamate, and GABA receptors antagonists were also reduced by NRG1 beta. Thus, short-term as well as long-term effects of NRG must be taken into consideration in studies of ACh receptor-mediated synaptic efficacy in the CNS.