Resuscitation of brain neurons in the presence of Ca2+ after toxic NMDA-receptor activity.

Cultured cerebellar granule cells were subjected to toxic activation of the NMDA receptor that was terminated by MK-801. Subsequent resuscitation experiments were mostly conducted in the presence of a physiological concentration of Ca2+. Addition of pyruvate and inorganic phosphate, in addition to glucose, which was always present, rescued approximately 40% of the dying neurons. La3+ and ruthenium red were also effective resuscitating agents. The combination of pyruvate, inorganic phosphate, and ruthenium red rescued 65% of the dying neurons. Parallel studies with 45Ca indicated that La3+ and ruthenium red facilitated the decrease of 45Ca in the neurons, whereas inorganic phosphate, supported by energy-yielding pyruvate, formed perhaps, a less harmful Ca complex inside the neurons.