Reduced voltage-dependent Ca2+ signaling in CA1 neurons after brief ischemia in gerbils

An initial overload of intracellular Ca2+ plays a critical role in the dela yed death of hippocampal CA1 neurons that die a few days after transient is chemia. Without direct evidence, the prevailing hypothesis has been that Ca 2+ overload may recur until cell death. Here, we report the first measureme nts of intracellular Ca2+ in living CA1 neurons within brain slices prepare d 1, 2, and 3 days after transient (5 min) ischemia. With no sign of ongoin g Ca2+ overload, voltage-dependent Ca2+ transients were actually reduced af ter 2-3 days of reperfusion. Resting Ca2+ levels and recovery rate after lo ading were similar to neurons receiving no ischemic insult. The tetrodotoxi n-insensitive Ca spike, normally generated by these neurons, was absent at 2 days postischemia, as was a large fraction of Ca2+-dependent spike train adaptation. These surprising findings may lead to a new perspective on dela yed neuronal death and intervention.