Stimulus- and amino acid-induced calcium and potassium changes in rat neocortex

R. Pumain and U. Heinemann Local changes in extracellular concentration of calcium ions, [Ca2+]o, and potassium ions, [K+]o, elicited through ionophoretic applications of the excitatory amino acids glutamate (Glu) and aspartate (Asp) or through cortical surface stimulations were measured in the rat motor cortex using paired ion-selective microelectrodes. Glu or Asp applications produced dose-dependent decreases in [Ca2+]o from a base line of 1.25 mM to as low as 0.08 mM and increases in [K+]o from 2.8 mM to as high as 13.3 mM. These ionic changes were accompanied by negative DC potential shifts of up to 15 mV. [K+]o changes were practically constant in all cortical layers, whereas [Ca2+]o changes were variable with depth, showing two localized marked maximums. One was observed in the superficial layers, 150-300 microns below cortical surface and the second at 1,100-1,300 microns, in a region corresponding roughly to layer V. Application of tetrodotoxin (TTX) onto the cortical surface abolished stimulus-evoked ionic changes, whereas amino acid-induced [Ca2+]o changes remained practically unaltered, and [K+]o changes were reduced by 20% on average. Selective degeneration of the pyramidal tract neurons was induced by performing chronic lesions of the pyramidal tract at the bulbar level. In these conditions, laminar profiles of amino acid-induced [Ca2+]o changes were considerably altered in the corresponding motor cortex. The maximum Ca2+ changes were then reduced by two-thirds, and the [Ca2+]o signals were practically constant throughout the cortex. Local cobalt (Co2+) or manganese (Mn2+) applications could abolish amino acid-evoked [Ca2+]o changes, whereas most of the [K+]o changes persisted. gamma-Aminobutyric acid applications could decrease [Ca2+]o signals to a large extent, whereas [K+]o changes were diminished by only 15-25% on average. These results show that the putative neurotransmitters Glu and Asp induce significant changes in [Ca2+]o and [K+]o in the rat cerebral cortex and indicate the possible origin of the ion fluxes in terms of neuronal elements and ionic channels: in particular, they indicate that the major part of the amino acid-induced [Ca2+]o maximum decreases can be ascribed to Ca2+ movements through channels located very likely on the pyramidal tract neurons in the motor cortex. They also indicate that significant reductions of the extracellular space volume occur during excitatory amino acid applications.