Chemical hypoxia in hippocampal pyramidal cells affects membrane potentialdifferentially 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 CAI neurons and to eluci date the reason for previously found differences in the reaction to hypoxia in these cells. Recordings were performed in brain slices from 8-19-day-ol d rats with whole-cell patch clamp on cells identified with near-infrared v ideo microscopy. Cyanide (0.1-2.0 mM) caused different responses depending on the resting potential of the cells: hyperpolarization (or an initial dep olarization followed by hyperpolarization) was generally seen in cells with less negative resting potential (-56 +/-6.1 mV), and depolarization in cel ls with more negative resting potential (-62 +/-3.4 mV). After 10 min in cy anide the membrane potential in all cells had reached approximately the sam e level (-62 +/-5.8 m.V), the direction and size of the voltage response ha ving 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 injecti on (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 muM) resulted in pronounced depolarization d uring cyanide perfusion, and potentiated the hyperpolarization during wash out indicating that this part of the effect is not dependent on a reactivat ion of the Na/K pump. In conclusion, chemical hypoxia with cyanide changes the membrane potential in CAI cells in size and direction depending on the original resting poten tial of the cells. The present findings suggested that cyanide activated no t only K+ channels but in addition increased a Na+ current which has a more positive equilibrium potential. (C) 2001 IBRO. Published by Elsevier Scien ce Ltd. All rights reserved.