Protein Kinase C Activation Decreases Activity-Dependent Attenuation of Dendritic Na+ Current in Hippocampal CA1 Pyramidal Neurons

Abstract

Action potentials recorded from the soma of CA1 pyramidal neurons remain relatively uniform in amplitude during repetitive firing. In contrast, the amplitudes of back-propagating action potentials in dendrites decrease progressively during a spike train. This activity-dependent decrease in amplitude is dependent on the frequency of firing during the train and distance from the soma. Previously, we described a property of Na+ channels that provides a plausible mechanism for the activity dependence of the amplitude of the dendritic action potentials: available Na+ current decreases during trains of action potentials through an inactivation, distinct from fast inactivation, that appears rapid in onset, but slow and voltage-dependent in its recovery. In this study we found that activation of protein kinase C by phorbol esters decreased this activity-dependent inactivation of pharmacologically isolated Na+ current in cell-attached dendritic, but not somatic, patches. Similarly in whole cell recordings phorbol esters decreased the attenuation of back-propagating dendritic action potentials during trains. These results indicate a novel effect of protein kinase C on the dendritic Na+ channel and further support the hypothesis that the activity dependence of the dendritic action potentials is derived from the inactivation properties of Na+ channels.