Effects of N ‐Methyl‐d‐Aspartate on [Ca 2+ ] i and the Energy State in the Brain by 19 F‐ and 31 P‐Nuclear Magnetic Resonance Spectroscopy

The effects of N ‐methyl‐d‐aspartate (NMDA) on the free intracellular Ca 2+ concentration ([Ca 2+ ] i ) and the energy state in superfused cerebral cortical slices have teen studied using 19 F‐ and 31 P‐nuclear magnetic resonance spectroscopy. [Ca 2+ ] i was measured using the calcium indicator 1,2‐bis(2‐amino‐5‐fluorophenoxy)ethane‐ N.N.N′.N′ ‐tetraacetic acid (5FBAPTA). NMDA (10 μ M ) in the absence of extracellular Mg 2+ caused the expected rise in [Ca 2+ ] i but produced an impairment of the energy state: the phosphocreatine (PCr) content was decreased by 42%, and the P i /PCr ratio was increased by 55%. There was no detectable change in ATP or free intracellular Mg 2+ concentration. Increasing the NMDA concentration in the superfusing medium to 100 or 400 μ M caused no further increase in [Ca 2+ ] i or further decrease in PCr content, but the P i /PCr ratio continued to rise. The impairment of the energy state preceded the effect on [Ca 2+ ] i , and these changes were irreversible on return to control conditions. Repeating the experiments in the presence of 1.2 m M extracellular Mg 2+ resulted in similar changes in the energy state, with no change in [Ca 2+ ] i . The possibilities that the effects were due to membrane depolarisation or to the presence of 5FBAPTA within the tissues were eliminated. The results suggest that low concentrations (10 μ M ) of NMDA produce an impaired energy state independent of the presence of extracellular Mg 2+ and that the decreased energy state is not due to the changes in [Ca 2+ ] i , which are seen only in the absence of extracellular Mg 2+ .