Department of Biomedical Engineering and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.
Trends Neurosci. 2010 Sep;33(9):415-23. doi: 10.1016/j.tins.2010.06.004.
The voltage- and Ca(2+)-activated K(+) (BK) channels are involved in the regulation of neurotransmitter release and neuronal excitability. Structurally, BK channels are homologous to voltage- and ligand-gated K(+) channels, having a voltage sensor and pore as the membrane-spanning domain and a cytosolic domain containing metal binding sites. Recently published electron cryomicroscopy (cryo-EM) and X-ray crystallographic structures of the BK channel provided the first glimpse into the assembly of these domains, corroborating the close interactions among these domains during channel gating that have been suggested by functional studies. This review discusses these latest findings and an emerging new understanding about BK channel gating and implications for diseases such as epilepsy, in which mutations in BK channel genes have been associated.
电压和 Ca(2+)-激活的 K(+) (BK) 通道参与神经递质释放和神经元兴奋性的调节。在结构上，BK 通道与电压门控和配体门控 K(+) 通道具有同源性，具有电压传感器和作为跨膜域的孔以及包含金属结合位点的胞质域。最近发表的 BK 通道电子冷冻显微镜 (cryo-EM) 和 X 射线晶体结构首次揭示了这些结构域的组装，证实了功能研究中提出的通道门控过程中这些结构域之间的紧密相互作用。本综述讨论了这些最新发现以及对 BK 通道门控的新认识及其对疾病的影响，例如癫痫，BK 通道基因的突变与癫痫有关。
