Department of Biology, Miami University, Oxford, Ohio 45056.
Division of Cardiology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri 63130.
J Neurosci. 2024 Jul 17;44(29):e2396232024. doi: 10.1523/JNEUROSCI.2396-23.2024.
The resurgent sodium current (I) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I is thought to drive high rates of repetitive neuronal firing. However, I is often studied in combination with the persistent or noninactivating portion of sodium currents (I). We used dynamic clamp to test how I and I individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned I does not scale repetitive firing rates due to its rapid decay at subthreshold voltages and that subthreshold I is critical in regulating neuronal firing rate. Adjustments to the voltage-gated sodium conductance model used in these studies revealed I and I 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 I and Purkinje neuron repetitive firing rates.
复活的钠电流 (I) 在膜复极化时激活，例如在神经元动作电位的下降时。由于其独特的激活特性，I 被认为驱动神经元高频重复放电。然而，I 通常与钠电流的持续或非失活部分 (I) 一起研究。我们使用动态钳位来测试 I 和 I 单独如何影响雄性和雌性小鼠成年小脑浦肯野神经元的重复放电。我们发现，由于 I 在亚阈电压下迅速衰减，因此它不会调节重复放电率，并且亚阈 I 对于调节神经元放电率至关重要。对这些研究中使用的电压门控钠电导模型的调整表明，通过调整慢失活动力学状态下的占据度，可以反向调节 I 和 I。结合其他动态钳位实验，这些数据表明钠通道慢失活的调节可以精细调节 I 和浦肯野神经元的重复放电率。
