Calcium Influx is Responsible for Afterdepolarizations in Rat Hippocampal Dentate Granule Cells

ABSTRACT

Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of Na+ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic Na+ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about -49.04 +/- 1.69 mV (n=43, mean +/- SD) and lasting 3~7 ms. Increase of extracellular Ca2+ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A K+ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM Ca2+ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external Ca2+, even in the presence of 4-AP (2 mM). A Na+ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular Ca2+ influx contributes to the generation of ADP in granule cells.