Figure 6.

In vitro KA model: Kv1.1 channel upregulation in DG cells is reversible and neuroprotective. (A) Organotypic hippocampal slice cultures (OHCs) prepared from P2 mouse pups were treated after 7 days in vitro (DIV) either with normal medium (NaCl) or with 15 μM kainate (KA). Time-matched results were pooled into two periods: the acute post-KA (or post-NaCl) period (8–11 DIV) and the recovery period (18–21 DIV). (B) The AP response delays of cultured DG cells were strongly enhanced in KA vs. control slices during the acute period (compare upper and lower Post-traces, and blue Post-NaCl and orange Post-KA bars, respectively). Importantly, during the recovery period, the response delays of KA-incubated slices returned to small NaCl-like values (compare upper and lower Recovery traces and orange Post-KA and orange Recovery-KA bars, respectively). Scale bars, 20 mV, 0.5 s. Current steps: NaCl, 70 pA; KA, 40 pA. (C) Staining with propidium iodide (PI), a cell death marker, showed that KA induced widespread cell death of hippocampal cells (left, Post-KA subpanel), which was quantified in the DG cell layer (white border, see Methods). The addition of Kv1 blocker DTX in the acute phase only mildly affected cell death under control conditions (NaCl, NaCl/DTX) but led to a massive increase in cell death in the DG cell layer (left panel, Post-KA/DTX subpanel, and right panel). These results indicate that the presence of functional Kv1 channels has a neuroprotective effect for DG cells.