A Negative Slope Conductance of the Persistent Sodium Current Prolongs Subthreshold Depolarizations

Abstract

Neuronal subthreshold voltage-dependent currents determine membrane properties such as the input resistance (R_in) and the membrane time constant (τ_m) in the subthreshold range. In contrast with classical cable theory predictions, the persistent sodium current (I_NaP), a non-inactivating mode of the voltage-dependent sodium current, paradoxically increases R_in and τ_m when activated. Furthermore, this current amplifies and prolongs synaptic currents in the subthreshold range. Here, using a computational neuronal model, we showed that the creation of a region of negative slope conductance by I_NaP activation is responsible for these effects and the ability of the negative slope conductance to amplify and prolong R_in and τ_m relies on the fast activation of I_NaP. Using dynamic clamp in hippocampal CA1 pyramidal neurons in brain slices, we showed that the effects of I_NaP on R_in and τ_m can be recovered by applying an artificial I_NaP after blocking endogenous I_NaP with tetrodotoxin. Furthermore, we showed that injection of a pure negative conductance is enough to reproduce the effects of I_NaP on R_in and τ_m and is also able to prolong artificial excitatory post synaptic currents. Since both the negative slope conductance and the almost instantaneous activation are critical for producing these effects, the I_NaP is an ideal current for boosting the amplitude and duration of excitatory post synaptic currents near the action potential threshold.