Fast-inactivating current through these channels plays a central role in the initiation and propagation of action potentials ( Hodgkin and Huxley, 1952 Stuart and Sakmann, 1994). Somata and processes of cortical pyramidal neurons contain an inhomogeneously distributed mixture of molecularly distinct voltage-gated Na + channels ( Bean, 2007). Finally, we show that the presence of endogenous polyamines significantly constrains I NaP availability in all compartments of nondialyzed cortical neurons. We found that at near-threshold voltages I NaP originates predominately from the axon, because of the distinctive voltage dependence of the underlying channels and not because of their high density. Using high-speed fluorescence Na + imaging and electrical recordings, we reconstructed the I NaP in soma and processes of cortical pyramidal neurons. Its subcellular distribution and generation mechanisms are, however, elusive. In cortical neurons, persistent current ( I NaP) plays a prominent role in many important functions. However, a fraction of the sodium current does not inactivate.

SIGNIFICANCE STATEMENT The most salient characteristic of neuronal sodium channels is fast inactivation. Finally, we show that endogenous polyamines constrain I NaP availability in both somatodendritic and axonal compartments of nondialyzed cortical neurons. This difference in voltage dependence explains why, at functionally critical subthreshold voltages, most I NaP originates in the AIS. Although the density of channels underlying I NaP 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. We found that in all neuronal compartments, the relationship between persistent Na + conductance and membrane voltage has the shape of a Boltzmann function. Using high-speed fluorescence Na + imaging and whole-cell recordings in brain slices obtained from mice of either sex, we reconstructed the I NaP elicited by slow voltage ramps in soma and processes of cortical pyramidal neurons. The subcellular distribution of channels responsible for I NaP and the mechanisms that render them persistent are not known. Although relatively quite small, I NaP is active at subthreshold voltages and therefore plays an important role in neuronal input–output processing. Cortical pyramidal neurons possess a persistent Na + current ( I NaP), which, in contrast to the larger transient current, does not undergo rapid inactivation.

Experience Points by N.A. Melamed