Gu Yuanzheng, Servello Dustin, Han Zhi, Lalchandani Rupa R, Ding Jun B, Huang Kun, Gu Chen
Department of Biological Chemistry and Pharmacology, The Ohio State University, 182 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210, USA.
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
iScience. 2018 Nov 30;9:120-137. doi: 10.1016/j.isci.2018.10.014. Epub 2018 Oct 18.
Fast-spiking (FS) neurons can fire action potentials (APs) up to 1,000 Hz and play key roles in vital functions such as sound location, motor coordination, and cognition. Here we report that the concerted actions of Kv3 voltage-gated K (Kv) and Na (Nav) channels are sufficient and necessary for inducing and maintaining FS. Voltage-clamp analysis revealed a robust correlation between the Kv3/Nav current ratio and FS. Expressing Kv3 channels alone could convert ∼30%-60% slow-spiking (SS) neurons to FS in culture. In contrast, co-expression of either Nav1.2 or Nav1.6 together with Kv3.1 or Kv3.3, but not alone or with Kv1.2, converted SS to FS with 100% efficiency. Furthermore, RNA-sequencing-based genome-wide analysis revealed that the Kv3/Nav ratio and Kv3 expression levels strongly correlated with the maximal AP frequencies. Therefore, FS is established by the properly balanced activities of Kv3 and Nav channels and could be further fine-tuned by channel biophysical features and localization patterns.
快速发放（FS）神经元能够以高达1000赫兹的频率发放动作电位（AP），并在诸如声音定位、运动协调和认知等重要功能中发挥关键作用。在此，我们报告Kv3电压门控钾（Kv）通道和钠（Nav）通道的协同作用对于诱导和维持FS是充分且必要的。电压钳分析揭示了Kv3/Nav电流比率与FS之间存在很强的相关性。在培养物中单独表达Kv3通道可使约30% - 60%的慢发放（SS）神经元转变为FS神经元。相比之下，Nav1.2或Nav1.6与Kv3.1或Kv3.3共同表达，但单独或与Kv1.2共同表达则不能，可100%有效地将SS神经元转变为FS神经元。此外，基于RNA测序的全基因组分析表明，Kv3/Nav比率和Kv3表达水平与最大AP频率密切相关。因此，FS是由Kv3和Nav通道适当平衡的活动所建立的，并且可以通过通道生物物理特性和定位模式进一步微调。
