Figure 2.

Changes in neuronal membrane properties following glutamate (GLU) excitotoxicity are prevented by ketones (KB). KB were administered as a cocktail in a 1:1 concentration ratio of BHB to ACA (either 0.1 mM or 1.0 mM each). (A) Exposure to GLU (10 μM ) for 10 min (short horizontal bar) alone resulted in an initial, small depolarization followed by a sharp, larger increase of the membrane potential (V_m) without return to baseline despite a 10 min washout period. The same protocol was used in the presence of BHB and ACA (1 mM each; long horizontal bar) but in this case, GLU induced a stable, depolarizing response with return of V_m to baseline after discontinuation of the application. (B) GLU (n = 13) significantly reduced R_m relative to control (CTRL; n = 8; p = 0.02). Following the addition of the 1 mM KB combination 20 (N = 13) or catalase 250 U/ml (n = 6), but not the 0.1 mM KB combination (n = 12), R_m was significantly higher than in cases exposed to GLU alone (p < 0.01). (C) The electrophysiological changes induced by GLU could not be attributed to morphological changes or technical difficulties. The two-dimensional surface area of the neuron exposed to GLU alone (in the absence of any fluorescent dyes) was unchanged by the experimental protocol and the position of the recording electrode was stable throughout the experiment. Neurons in all treatment groups displayed similar surface areas at the beginning and at the end of the experiments.