Persistent Sodium Currents in Mesencephalic V Neurons Participate in Burst Generation and Control of Membrane Excitability

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Abstract
The functional and biophysical properties of a persistent sodium current ( INaP) 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. INaPactivated around −76 mV and peaked at −48 mV, with V1/2of −58.7 mV. Ramp voltage-clamp protocols showed that INaPundergoes time- as well as voltage-dependent inactivation and recovery from inactivation in the range of several seconds (τonset= 2.04 s, τrecov= 2.21 s). Riluzole (≤5 μM) substantially reduced INaP, membrane resonance, postinhibitory rebound (PIR), and subthreshold oscillations, and completely blocked bursting, but produced modest effects on the fast transient Na+current ( INaT). Before complete cessation, burst cycle duration was increased substantially, while modest and inconsistent changes in burst duration were observed. The properties of the INaTwere obtained and revealed that the amplitude and voltage dependence of the resulting “window current” were not consistent with those of the observed INaPrecorded in the same neurons. This suggests an additional mechanism for the origin of INaP. 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 gNaPparameters indicate that INaPis critical for control of subthreshold and suprathreshold Mes V neuron membrane excitability and burst generation.