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.
Competing Interests: The authors declare no competing financial interests.
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