Persistent sodium currents in mesencephalic V neurons participate in burst generation and control of membrane excitability

The functional and biophysical properties of a persistent sodium current (I _NaP) previously proposed to participate in the generation of subthreshold oscillations and burst discharge in mesencephalic trigeminal sensory neurons (Mes V) were investigated in brain stem slices (rats, p7-p12) using whole cell patch-clamp methods. I _NaP activated around -76 mV and peaked at -48 mV, with V _1/2 of -58.7 mV. Ramp voltage-clamp protocols showed that I _NaP undergoes time- as well as voltage-dependent inactivation and recovery from inactivation in the range of several seconds (τ _onset = 2.04 s, τ _recov = 2.21 s). Riluzole (≤5 μM) substantially reduced I _NaP, membrane resonance, postinhibitory rebound (PIR), and subthreshold oscillations, and completely blocked bursting, but produced modest effects on the fast transient Na ⁺ current (I _NaT). Before complete cessation, burst cycle duration was increased substantially, while modest and inconsistent changes in burst duration were observed. The properties of the I _NaT were obtained and revealed that the amplitude and voltage dependence of the resulting "window current" were not consistent with those of the observed I _NaP recorded in the same neurons. This suggests an additional mechanism for the origin of I _NaP. A neuronal model was constructed using Hodgkin-Huxley parameters obtained experimentally for Na ⁺ and K ⁺ currents that simulated the experimentally observed membrane resonance, subthreshold oscillations, bursting, and PIR. Alterations in the model g _NaP parameters indicate that I _NaP is critical for control of subthreshold and suprathreshold Mes V neuron membrane excitability and burst generation.