"... Ramps were applied to CA1 pyramidal neurons from male rats in vitro (slice electrophysiology) and in silico (multi-compartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared to somatic ramps. We incorporated a four-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in closed states, which comprise the available pool..."
Upchurch CM, Combe CL, C Knowlton, V Rousseau, Gasparini S, Canavier CC (2021) Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Cells J Neuroscience [PubMed]