PDF(Pubmed)
Abstract：
The resurgent sodium current (INaR) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, INaR is thought to drive high rates of repetitive neuronal firing. However, INaR is often studied in combination with the persistent or noninactivating portion of sodium currents (INaP). We used dynamic clamp to test how INaR and INaP individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned INaR does not scale repetitive firing rates due to its rapid decay at subthreshold voltages and that subthreshold INaP is critical in regulating neuronal firing rate. Adjustments to the voltage-gated sodium conductance model used in these studies revealed INaP and INaR can be inversely scaled by adjusting occupancy in the slow-inactivated kinetic state. Together with additional dynamic clamp experiments, these data suggest the regulation of sodium channel slow inactivation can fine-tune INaP and Purkinje neuron repetitive firing rates.
摘要：
恢复钠电流（INaR）激活膜复极化，例如在神经元动作电位下降期间。由于其独特的激活特性，INaR被认为驱动高速率的重复神经元放电。然而,INaR通常与钠电流（INaP）的持续或非失活部分结合进行研究。我们使用动态钳夹测试INaR和INaP如何单独影响雄性和雌性小鼠成年小脑Purkinje神经元的重复放电。我们了解到，由于INaR在亚阈值电压下快速衰减，因此无法缩放重复点火率，亚阈值INaP对调节神经元放电率至关重要。对这些研究中使用的Nav电导模型的调整表明，INaP和INaR可以通过调整缓慢失活动力学状态下的占有率来反向缩放。加上额外的动态夹具实验，这些数据表明钠通道缓慢失活的调节可以微调INaP和Purkinje神经元重复放电率。跨神经元细胞类型的重要性声明，复苏的钠电流（INaR-）通常与驱动高速率的重复放电有关。使用动态夹具，我们确定INaR对驱动后续动作电位无效，并且亚阈值持续钠电流（INaP）是缩放重复激发率的关键参数。我们提出在天然神经元中测量的INaR可能反映了INaP大小被微调的机制。
