A Reinterpretation of the Relationship between Persistent and Resurgent Sodium Currents.

The resurgent sodium current (I NaR ) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I NaR is thought to drive high rates of repetitive neuronal firing. However, I NaR is often studied in combination with the persistent or noninactivating portion of sodium currents (I NaP ). We used dynamic clamp to test how I NaR and I NaP individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned I NaR does not scale repetitive firing rates due to its rapid decay at subthreshold voltages and that subthreshold I NaP is critical in regulating neuronal firing rate. Adjustments to the voltage-gated sodium conductance model used in these studies revealed I NaP and I NaR 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 NaP and Purkinje neuron repetitive firing rates.