The Creation of A Negative Slope Conductance Region by the activation of The Persistent Sodium Current Prolongs Near-Threshold Synaptic Potentials

Abstract

ABSTRACTA change of the input resistance (Rin) of the neuron involves a change in the membrane conductances by opening and closing of ion channels. In passive membranes, i.e., membranes with only linear leak conductances, the increase or decrease of these conductances leads to a decrease or increase of the Rin and the membrane time constant (τm). However, the presence of subthreshold voltage dependent currents can produce non-linear effects generating deviations from this relationship, especially the contradictory effect of negative conductances, as produced by the sodium-persistent current (INaP), on the Rin. In this work we aimed to analyze experimentally and theoretically the impact of the negative conductance produced by INaP on Rin. Experiments of whole-cell patch-clamp conducted in CA1 hippocampus pyramidal cells from brain slices showed a paradoxical voltage-dependent decrease of the Rin and the τm in subthreshold membrane potentials close to the firing threshold after the perfusion with TTX, which inhibits INaP. This effect is postulated to be a result of the negative slope conductance in the subthreshold region produced by this conductance. The analysis of the experimental data, together with simulations found that the slope conductance of INaP is negative for subthreshold membrane potentials and its magnitude is voltage dependent in the same range observed for the voltage-dependence of Rin and τm. The injection of an artificial INaP using dynamic-clamp in the presence of TTX restored the Rin and τm to its original values. Additionally the injection of an artificial leak current with a negative conductance in the presence of TTX restored the Rin and τm as the artificial Inap did. On the other hand, the injection of an artificial leak current with a positive conductance in the presence of TTX had no effect on the Rin and τm. We conclude that INaP increases the Rin and τm by the negative slope conductance observed in its non-monotonic I-V relationship. These results demonstrate that the effect of Inap on Rin and τm is stronger in potentials near the firing threshold, which could potentiate the temporal summation of the EPSPs increasing their temporal integration and facilitating action potential firing. Because of its negative slope conductance, INaP is more effective in increasing excitability near threshold than a depolarizing leak current.