CHANGES OF EXTRACELLULAR CALCIUM-CONCENTRATION INDUCED BY APPLICATION OF EXCITATORY AMINO-ACIDS IN THE HUMAN NEOCORTEX IN-VITRO

The influence of the glutamate subreceptor agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydrooxy-5-methyl-4-isoxazolepropionic acid (AMPA) on cortical field potentials and on changes in extracellular free calcium concentration ([Ca2+](o)) was tested on human neocortical slices (eleven from nine different patients). The tissue used was a small portion of that which is normally removed for the treatment of a brain tumor. [Ca2+](o) and field potentials were measured by Ca2+-selective microelec trodes. Local pressure-microejection of NMDA (100 mu mol/l)- and AMPA (1 mmol/l)-induced negative field potentials with maximal amplitudes of 0.9 +/- 0.1 mV (11 slices, mean +/- S.E.M.) and 1.0 +/- 0.1 mV (nine slices), respectively. The negative field potentials induced by NMDA were accompanied by monophasic decreases of [Ca2+](o) (0.8 +/- 0.1 mmol/l, nine slices). AMPA elicited no (three slices) or only minor decreases of [Ca2+](o) (0.2 +/- 0.1 mmol/l, five slices). The responses to the glutamate subreceptor agonists NMDA and AMPA were reversibly depressed by adding their specific antagonists DL-2-amino-5-phosphonovalerate (APV, 100 mu mol/l, six slices) and 6-cyano-7-nitroquinoxalin-2,3-dion (CNQX, 5 mu mol/l, four slices), respectively. The results correspond to findings in animal experiments and are consistent with the interpretation that in the human neocortex the Ca2+ permeability of channels gated by NMDA is higher than those gated by AMPA.