Brown, S. P.; Lawson, R. J.; Moreno, J. D.; Ransdell, J. L.

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 often thought to support high rates of repetitive neuronal firing. However, INaR is typically studied in combination with the persistent or non-inactivating portion of sodium currents (INaP). We used dynamic clamp to test how INaR and INaP individually affect repetitive firing in adult cerebellar Purkinje neurons. We learned INaR has no effect on repetitive firing rates due to its rapid decay at subthreshold voltages, and that subthreshold INaP is critical in regulating neuronal firing rate. Using computational modeling and dynamic clamp experiments, we found INaP and INaR can be inversely scaled by adjusting occupancy in a slow inactivated kinetic state. Thus, by reducing Nav channel slow inactivation, INaR is reduced and INaP is increased, which drives higher rates of Purkinje neuron firing.