Protein kinase C bound with A-kinase anchoring protein is involved in muscarinic receptor-activated modulation of M-type KCNQ potassium channels
Protein kinase C bound with A-kinase anchoring protein is involved in muscarinic receptor-activated modulation of M-type KCNQ potassium channels
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DOI：
10.1016/j.neures.2004.11.009
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发表时间：
2005-03-01
影响因子：
2.9
通讯作者：
Robbins, J
中科院分区：
文献类型：
--
作者：
Higashida, H;Hoshi, N;Robbins, J
在神经节后神经元和中枢神经元中，关闭M/KCNQ钾通道的第二个信使在过去的25年里一直是神经科学领域的一个谜。然而，最近发现了从毒瘤碱乙酰胆碱受体（mAChR）刺激到M/ kcnq电流抑制的途径的细节。一个关键分子是A激酶锚定蛋白（AKAP，人的AKAP79或其大鼠同源物AKAP150），它与蛋白激酶C （PKC和KCNQ通道）形成三聚体复合物。AKAP79或150作为一个适配器，将锚定的c激酶带到底物KCNQ通道，以允许丝氨酸残基的快速和“最终”磷酸化，从而避免信号分散。因此，这些发现表明，machr诱导的短期调节（或记忆）确实发生在已经整合良好的分子复合体中，而没有伴随Hebbian突触可塑性。然而，在这一特性得到证实之前，许多其他影响m电流的调制器仍有待解决，这是一个有趣的问题。(C) 2004爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
The second messenger for closure of M/KCNQ potassium channels in post-ganglionic neurons and central neurons had remained as a 'mystery in the neuroscience field' for over 25 years. However, recently the details of the pathway leading from muscarinic acetylcholine receptor (mAChR)-stimulation to suppression of the M/KCNQ-current were discovered. A key molecule is A-kinase anchoring protein (AKAP; AKAP79 in human, or its rat homolog, AKAP150) which forms a trimeric complex with protein kinase C (PKC and KCNQ channels. AKAP79 or 150 serves as an adapter that brings the anchored C-kinase to the substrate KCNQ channel to permit the rapid and 'definitive' phosphorylation of serine residues, resulting in avoidance of signal dispersion. Thus, these findings suggest that mAChR-induced short-term modulation (or memory) does occur within the already well-integrated molecular complex, without accompanying Hebbian synapse plasticity. However, before this identity is confirmed, many other modulators which affect M-currents remain to be addressed as intriguing issues. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.