PROLONGED SODIUM-CHANNEL INACTIVATION CONTRIBUTES TO DENDRITIC ACTION-POTENTIAL ATTENUATION IN HIPPOCAMPAL PYRAMIDAL NEURONS

During low-frequency firing, action potentials actively invade the den drites of CA1 pyramidal neurons. At higher firing rates, however, acti vity-dependent processes result in the attenuation of back-propagating action potentials, and propagation failures occur at some dendritic b ranch points. We tested two major hypotheses related to this activity- dependent attenuation of back-propagating action potentials: (1) that it is mediated by a prolonged form of sodium channel inactivation and (2) that it is mediated by a persistent dendritic shunt activated by b ack-propagating action potentials. We found no evidence for a persiste nt shunt, but we did find that cumulative, prolonged inactivation of s odium channels develops during repetitive action potential firing. Thi s inactivation is significant after a single action potential and cont inues to develop during several action potentials thereafter, until a steady-state sodium current is established. Recovery from this form of inactivation is much slower than its induction, but recovery can be a ccelerated by hyperpolarization. The similarity of these properties to the time and voltage dependence of attenuation and recovery of dendri tic action potentials suggests that dendritic sodium channel inactivat ion contributes to the activity dependence of action potential back-pr opagation in CA1 neurons. Hence, the biophysical properties of dendrit ic sodium channels will be important determinants of action potential- mediated effects on synaptic integration and plasticity in hippocampal neurons.