Properties of slow, cumulative sodium channel inactivation in rat hippocampal CA1 pyramidal neurons

Sodium channels in the somata and dendrites of hippocampal CAI pyramidal ne urons undergo a form of long-lasting, cumulative inactivation that is invol ved in regulating back-propagating action potential amplitude and can influ ence dendritic excitation. Using cell-attached patch-pipette recordings in the somata and apical dendrites of CA1 pyramidal neurons, we determined the properties of slow inactivation on response to trains of brief depolarizat ions. We find that the amount of slow inactivation gradually increases as a function of distance from the soma. Slow inactivation is also frequency an d voltage dependent. Higher frequency depolarizations increase both the amo unt of slow inactivation and its rate of recovery. Hyperpolarized resting p otentials and larger command potentials accelerate recovery from slow inact ivation. We compare this form of slow inactivation to that reported in othe r cell types, using longer depolarizations, and construct a simplified biop hysical model to examine the possible gating mechanisms underlying slow ina ctivation. Our results suggest that sodium channels can enter slow inactiva tion rapidly from the open state during brief depolarizations or slowly fro m a fast inactivation state during longer depolarizations. Because of these properties of slow inactivation, sodium channels will modulate neuronal ex citability in a way that depends in a complicated manner on the resting pot ential and previous history of action potential firing.