Distinct developmental patterns in the expression of transient, persistent, and resurgent Na+ currents in entorhinal cortex layer-II neurons

Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major importance in determining the electrical properties of medial entorhinal cortex (mEC) layer-II neurons. Developmental changes in the ability of mEC layer-II stellate cells (SCs) to generate Na+-dependent, subthreshold electrical events have been reported between P14 and P18. In this study we examined the modifications occurring in the various components of VDSCs during postnatal development of mEC SCs. The transient, resurgent, and persistent Na+ currents (INaT, INaR, and INaP, respectively) showed distinct patterns of developmental expression in the time window considered (P5 to P24–27). All three currents prominently and steeply increased in absolute amplitude and conductance from P5 to at least P16. However, capacitive charge accumulation, an index of membrane surface area, also markedly increased in the same time window, and in the case of INaT the specific conductance per unit of accumulated capacitive charge remained relatively constant. By contrast, specific INaR and INaP conductances showed a significant tendency to increase, especially from P5 to P18. Neither INaR nor INaP represented a constant fraction of the total Na+ current at all developmental ages. Indeed, detectable levels of INaR and INaP were present in only ~ 20% and ~ 70%, respectively, of the cells on P5, and were observed in all cells only from P10 onwards. Moreover, the average INaR-to-INaT conductance ratio increased steadily from ~ 0.004 (P5) up to a plateau level of ~ 0.05 (P22+), whereas the INaP-to-INaT conductance ratio increased only from ~ 0.009 on P5 to ~ 0.02 on P22+. The relative increase in conductance ratio from P5 to P22 was significantly greater for INaR than for INaP, indicating that INaR expression starts later than that of INaP. These findings show that in mEC layer-II SCs the single functional components of the VDSC are regulated differentially from each other as far as their developmental expression is concerned.

► Sodium currents showed prominent changes between P5 and P20 in mEC stellate cells.
► The transient current (INaT) increased in absolute amplitude but not in density.
► Resurgent current (INaR) amplitude relative to INaT increased prominently.
► Persistent current (INaR) relative amplitude also increased, but less prominently.
► INaR and INaP time course of development differed at early ages (P5–P10).