Subcellular Distribution Of Persistent Sodium Conductance In Cortical Pyramidal Neurons

Cortical pyramidal neurons possess a persistent Na+ current (I-NaP) which, in contrast to the larger transient current, does not undergo rapid inactivation. Although relatively quite small, I-NaP is active at subthreshold voltages and therefore plays an important role in neuronal input-output processing. The subcellular distribution of channels responsible for I-NaP and the mechanisms which 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 I-NaP 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 I-NaP was about twofold lower in the axon initial segment (AIS) than in the soma, the axonal channels were activated by about 10 mV less depolarization than were somatic channels. This difference in voltage dependence explains why, at functionally critical subthreshold voltages, most I-NaP originates in the AIS. Finally, we show that endogenous polyamines constrain I-NaP availability in both somato-dendritic and axonal compartments of non-dialyzed cortical neurons.