Effect of hypoxia on calcium channels depends on extracellular calcium in CA1 hippocampal neurons.

Our previous studies have shown that short lasting hypoxia induces an increase of Ca(2+) influx into the cell through high voltage-activated Ca(2+) channels in hippocampal neurons. This effect was abolished by removing of free Ca(2+) from intracellular solution. The aim of this study was to compare hypoxic responses at different extracellular Ca(2+) concentrations ([Ca(2+)](e)) in hippocampal neurons to ascertain whether the hypoxic sensitivity is restricted to Ca(2+) ions. Whole-cell patch-clamp recordings were made from acutely dissociated CA1 hippocampal neurons of rats. Polarographic method for measurements of O(2) partial pressure was used. Here we found that at 2 mM [Ca(2+)](e) the hypoxic effect was significant (up to approximately 94%), whereas [Ca(2+)](e) elevations to 5 and 15 mM resulted in gradual decreasing of the effect. We found, that total Ca(2+) charge carried into the cell under the hypoxia was similar at all [Ca(2+)](e), whereas Ca(2+) charge carried at normoxia was different for different [Ca(2+)](e), being larger at higher [Ca(2+)](e). These data indicated a saturation of the hypoxic effect due to limitation in the channel conductance. Therefore, we suggested that the hypoxic effect can be connected with increase of channel conductance, and the level of channel conductance at normoxia can determine the amplitude of hypoxic effect.