Abstract

The hippocampus, a critical structure for learning and memory, is highly susceptible to changes in the extracellular ionic environment, particularly the concentration of potassium ions ($[K^+]_o$). Elevated $[K^+]_o$ is a hallmark of intense neuronal activity and pathological conditions like epilepsy, leading to widespread membrane depolarization and altered excitability. This study investigated the differential impact of increased $[K^+]_o$ on the electrophysiological properties of two principal hippocampal cell types: CA1 pyramidal cells and Dentate Gyrus (DG) granule cells. Using whole-cell patch-clamp recordings in acute hippocampal slices, we compared the spontaneous and evoked activity of these neurons under control and elevated $[K^+]_o$ conditions. Our findings reveal a distinct cell-type specific response. Increased $[K^+]_o$ significantly enhanced inward currents and shifted the current-voltage relationship to the right in both cell types, consistent with membrane depolarization. However, the magnitude of this effect was markedly greater in DG granule cells, which exhibited a 4- to 4.5-fold higher increase in inward and outward currents compared to CA1 pyramidal cells. This differential sensitivity suggests that DG granule cells are more vulnerable to excitability changes induced by potassium dysregulation. The results underscore a fundamental difference in the membrane biophysics and ion channel expression profiles between CA1 and DG neurons, providing critical insight into the mechanisms by which extracellular ion homeostasis regulates hippocampal network function and contributes to the differential susceptibility of these regions to hyperexcitability.