Higashida Haruhiro, Hoshi Naoto, Zhang Jia-Sheng, Yokoyama Shigeru, Hashii Minako, Jin Duo, Noda Mami, Robbins Jon
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
Neurosci Res. 2005 Mar;51(3):231-4. doi: 10.1016/j.neures.2004.11.009. Epub 2005 Jan 8.
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.
在节后神经元和中枢神经元中，M/KCNQ钾通道关闭的第二信使在超过25年的时间里一直是“神经科学领域的一个谜”。然而，最近发现了从毒蕈碱型乙酰胆碱受体（mAChR）刺激到抑制M/KCNQ电流的信号通路细节。一个关键分子是A激酶锚定蛋白（AKAP；人类中的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作为一种衔接蛋白，将锚定的C激酶带到底物KCNQ通道，使丝氨酸残基能够快速且“确定地”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）确实发生在已经充分整合的分子复合物中，而不伴有赫布突触可塑性。然而，在这一特性得到证实之前，许多其他影响M电流的调节剂仍有待作为有趣的问题加以探讨。
