Balanced Activity between Kv3 and Nav Channels Determines Fast-Spiking in Mammalian Central Neurons

作者：Gu, Yuanzheng; Servello, Dustin; Han, Zhi; Lalchandani, Rupa R.; Ding, Jun B.; Huang, Kun; Gu, Chen^*

来源：iScience, 2018, 9: 120-+.

DOI：10.1016/j.isci.2018.10.014

• ACTIVATED CATION CHANNELS
• RESURGENT SODIUM CURRENTS
• POTASSIUM-CHANNEL
• PURKINJE NEURONS
• DRAVET-SYNDROME
• SUBCELLULAR-LOCALIZATION
• MOTOR COORDINATION
• SUBUNIT KV3.1B
• ION CHANNELS
• K+ CHANNELS

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 similar to 30%similar to 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 Nay channels and could be further fine-tuned by channel biophysical features and localization patterns.

• 出版日期2018-11-30
• 单位深圳大学; 南开大学