The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture

Publisher Website
Google Scholar
Abstract
Neurons from brain and spinal cord of fetal mice were grown dissociated in monolayer cultures for 4-6 wk prior to electropharmacological analysis. Neurons were immersed in a Hanks balanced salt solution while drugs and ions were applied by pressure microperfusion during intracellular recordings obtained by conventional techniques. L-Glutamate and its analogs, L-aspartate, DL-homocysteate, N-methyl-D-aspartate and DL-ibotenate activated 2 distinct mechanisms of excitation. The primary effect was depolarization accomplished by an apparent decrease of neuron input conductance (Gm). In most instances an expected increase in Gm was observed, especially if membrane potential was reduced by tonic depolarization. Another glutamate analog, DL-kainate, never decreased Gm and invariably increased Gm at all membrane potentials tested. The decrease of Gm evoked by glutamate and related compounds was dependent on membrane potential. It was most pronounced at potentials near resting values (-40 to -60 mV) and diminished both with depolarization or hyperpolarization from this range. This apparent decrease favored the electrogenesis of regenerative potentials that were insensitive to tetrodotoxin. A voltage-dependent increase in Na and/or Ca conductance (GNa, GCa) or a decrease in K conductance is suggested to account for this decrease in Gm. Divalent cations (Mg2+ and Co2+) reduced the depolarizing actions of all amino acids except for those to kainate. The decrease in Gm was more sensitive to Mg2+ than was the increase of Gm. The receptor antagonist DL-.alpha.-aminoadipate blocked with changes in conductance and responses to all amino acids with the exception of those to kainate. The possible existence of multiple receptors for glutamate is also discussed.