A recent study of the effects of the persistent sodium current (INaP) on action potential generation during repetitive firing in CA1 hippocampal pyramidal neurons, revealed that INaP reduces the gain (slope) of the frequency- current relation (f/I curve), while shifting the f/I curve towards lower current intensities (Vervaeke et al, Neuron, 2006). The leftward shift of the f/I curve can readily be explained by the depolarizing effect of INaP. In contrast, the finding that INaP reduces the frequency gain (f/I slope), was unexpected and counterintuitive, and no satisfactory mechanistic explanation has so far been provided. Here, I propose an explanation that was developed without using new or unpublished data from computational modeling or experiments. In essence, INaP reduces the frequency gain (f/I slope) by changing the shape of the interspike (IS) trajectories through amplification of after-hyperpolarizations (AHPs) combined with generation of regenerative slow pre-potentials, thus hyperpolarizing the IS trajectories. Because INaP hyperpolarizes IS trajectories more at low than at high spike frequencies (due to difference in input resistance), K+ currents are reduced (due to reduced K+ driving force and K+ channel closure) more at low frequencies. This K+ current reduction adds to the direct excitatory effect of INaP, causing a larger leftward shift of the f/I curve at low frequencies than at high. Hence, the f/I slope is reduced by INaP. This hypothesis predicts that K+ currents are reduced, indirectly, by INaP more at low frequencies than at high. Effects of this type are likely to influence how synaptic input is translated into action potential frequency in pyramidal cells and other neurons with INaP or other persistent inward currents. [Supported by NFR]