The Shaker-related potassium channel Kv1.1 subunit has important implications for controlling neuronal excitabilities. A particular recoding by A-to-I RNA editing at I400 of Kv1.1 mRNA is an underestimated mechanism for fine-tuning the properties of Kv1.1-containing channels. Knowledge about functional differences between edited (I400V) and non-edited Kv1.1 isoforms is insufficient, especially in neurons. To understand their different roles, the two Kv1.1 isoforms were overexpressed in the prefrontal cortex via local adeno-associated virus-mediated gene delivery. The I400V isoform showed a higher competitiveness in membrane translocalization, but failed to reduce current-evoked discharges and showed weaker impact on spiking-frequency adaptation in the transduced neurons. The non-edited Kv1.1 overexpression led to slight elevations in both fast- and non-inactivating current components of macroscopic potassium current. By contrast, the I400V overexpression did not impact the fast-inactivating current component. Further isolation of Kv1.1-specific current by its specific blocker dendrotoxin-κ showed that both isoforms did result in significant increases in current amplitude, whereas the I400V was less efficient in contributing the fast-inactivating current component. Voltage-dependent properties of the fast-inactivating current component did not alter for both isoforms. For recovery kinetics, the I400V showed a significant acceleration of recovery from fast inactivation. The gene delivery of the I400V rather than the wild type exhibited anxiolytic activities, which was assessed by an open field test. These results suggest that the Kv1.1 RNA editing isoforms have different properties and outcomes, reflecting the functional and phenotypic significance of the Kv1.1 RNA editing in neurons.

Shaker 相关钾通道 Kv1.1 亚基对控制神经元兴奋性具有重要意义。在 Kv1.1 mRNA 的 I400 处通过 A-to-I RNA 编辑进行的特定重新编码是一种被低估的机制，用于微调包含 Kv1.1 的通道的特性。关于编辑 (I400V) 和非编辑 Kv1.1 亚型之间功能差异的知识是不够的，尤其是在神经元中。为了了解它们的不同作用，这两种 Kv1.1 亚型通过局部腺相关病毒介导的基因传递在前额叶皮层中过表达。I400V 异构体在膜转定位方面表现出更高的竞争力，但未能减少电流诱发的放电，并且对转导神经元的尖峰频率适应影响较弱。未经编辑的 Kv1. 1 过表达导致宏观钾电流的快速和非失活电流分量略有升高。相比之下，I400V 过表达不会影响快速失活的电流分量。Kv1.1 特异性电流通过其特异性阻断剂 dendrotoxin-κ 的进一步隔离表明，两种同工型确实导致电流幅度显着增加，而 I400V 在贡献快速失活电流分量方面效率较低。两种同工型的快速失活电流分量的电压相关特性没有改变。对于恢复动力学，I400V 显示出从快速失活中恢复的显着加速。I400V 的基因传递而不是野生型表现出抗焦虑活性，这是通过露天试验评估的。这些结果表明 Kv1.