Chemical hypoxia in hippocampal pyramidal cells affects membrane potential differentially depending on resting potential.

The aim of the present study was to analyze the effect of chemical hypoxia (cyanide) on the membrane potential of hippocampal CA1 neurons and to elucidate the reason for previously found differences in the reaction to hypoxia in these cells. Recordings were performed in brain slices from 8-19-day-old rats with whole-cell patch clamp on cells identified with near-infrared video microscopy. Cyanide (0.1-2.0 mM) caused different responses depending on the resting potential of the cells: hyperpolarization (or an initial depolarization followed by hyperpolarization) was generally seen in cells with less negative resting potential (-56+/-6.1 mV), and depolarization in cells with more negative resting potential (-62+/-3.4 mV). After 10 min in cyanide the membrane potential in all cells had reached approximately the same level (-62+/-5.8 mV), the direction and size of the voltage response having an inverse linear relation to the resting potential (k=-0.98, r=0.71). The direction of the cyanide response was not reversed by current injection (depolarization by 12 mV) in cells with more negative resting potential (-60+/-2.8 mV). Wash out of cyanide caused hyperpolarization in 70% of the cells. Presence of ouabain (2 microM) resulted in pronounced depolarization during cyanide perfusion, and potentiated the hyperpolarization during wash out indicating that this part of the effect is not dependent on a reactivation of the Na/K pump. In conclusion, chemical hypoxia with cyanide changes the membrane potential in CA1 cells in size and direction depending on the original resting potential of the cells. The present findings suggested that cyanide activated not only K+ channels but in addition increased a Na+ current which has a more positive equilibrium potential.