SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.
SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.
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DOI：
10.1016/j.bbamcr.2020.118834
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Bi X
中科院分区：
文献类型：
--
作者：
Sun J;Liu Y;Baudry M;Bi X
小电导钙激活钾通道（SKs）仅由细胞内Ca 2+激活，并且它们的激活导致钾流出，从而使膜电位复极化/超极化。因此，这些通道在突触传递中起关键作用，并因此在沿着表达它们的神经元回路的信息传递中起关键作用。SK广泛但不均匀地分布在中枢神经系统（CNS）中。SKs的激活需要亚微摩尔的细胞质Ca 2+浓度，这是在Ca 2+从细胞内Ca 2+库释放或通过Ca 2+渗透膜通道流入后达到的。SKs的Ca ~（2+）敏感性和突触水平均受蛋白激酶和磷酸酶以及降解途径的调节。SK反过来控制多个Ca 2+通道的活性。因此，它们在协调不同的Ca 2+信号通路和控制Ca 2+信号幅度和持续时间中起着关键作用。这篇综述强调了我们对SK2通道调节及其在正常脑功能中的作用的理解的最新进展，包括突触可塑性，学习和记忆以及节律活动。它还将讨论如何改变他们的表达和调节可能有助于各种大脑疾病，如安格尔曼综合征，阿尔茨海默病和帕金森病。
Small conductance calcium-activated potassium channels (SKs) are solely activated by intracellular Ca2+ and their activation leads to potassium efflux, thereby repolarizing/hyperpolarizing membrane potential. Thus, these channels play a critical role in synaptic transmission, and consequently in information transmission along the neuronal circuits expressing them. SKs are widely but not homogeneously distributed in the central nervous system (CNS). Activation of SKs requires submicromolar cytoplasmic Ca2+ concentrations, which are reached following either Ca2+ release from intracellular Ca2+ stores or influx through Ca2+ permeable membrane channels. Both Ca2+ sensitivity and synaptic levels of SKs are regulated by protein kinases and phosphatases, and degradation pathways. SKs in turn control the activity of multiple Ca2+ channels. They are therefore critically involved in coordinating diverse Ca2+ signaling pathways and controlling Ca2+ signal amplitude and duration. This review highlights recent advances in our understanding of the regulation of SK2 channels and of their roles in normal brain functions, including synaptic plasticity, learning and memory, and rhythmic activities. It will also discuss how alterations in their expression and regulation might contribute to various brain disorders such as Angelman Syndrome, Alzheimer’s disease and Parkinson’s disease.
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