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Subcellular Distribution of Persistent Sodium Conductance in Cortical Pyramidal Neurons

Cortical pyramidal neurons possess a persistent Na+ current (INaP), which, in contrast to the larger transient current, does not undergo rapid inactivation. Although relatively quite small, INaP is active at subthreshold voltages and therefore plays an important role in neuronal input–output processing. The subcellular distribution of channels responsible for INaP and the mechanisms that render them persistent are not known. Using high-speed fluorescence Na+ imaging and whole-cell recordings in brain slices obtained from mice of either sex, we reconstructed the INaP elicited by slow voltage ramps in soma and processes of cortical pyramidal neurons. We found that in all neuronal compartments, the relationship between persistent Na+ conductance and membrane voltage has the shape of a Boltzmann function. Although the density of channels underlying INaP was about twofold lower in the axon initial segment (AIS) than in the soma, the axonal channels were activated by ∼10 mV less depolarization than were somatic channels. This difference in voltage dependence explains why, at functionally critical subthreshold voltages, most INaP originates in the AIS. Finally, we show that endogenous polyamines constrain INaP availability in both somatodendritic and axonal compartments of nondialyzed cortical neurons. SIGNIFICANCE STATEMENT The most salient characteristic of neuronal sodium channels is fast inactivation. However, a fraction of the sodium current does not inactivate. In cortical neurons, persistent current (INaP) plays a prominent role in many important functions. Its subcellular distribution and generation mechanisms are, however, elusive. Using high-speed fluorescence Na+ imaging and electrical recordings, we reconstructed the INaP in soma and processes of cortical pyramidal neurons. We found that at near-threshold voltages INaP originates predominately from the axon, because of the distinctive voltage dependence of the underlying channels and not because of their high density. Finally, we show that the presence of endogenous polyamines significantly constrains INaP availability in all compartments of nondialyzed cortical neurons.