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 (tau(onset) = 2.04 s, tau(recov) = 2.21 s). Riluzole (<= 5 mu M) 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.