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.