The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture.
Neurones from brain and spinal cord of foetal mice were grown dissociated in monolayer cultures for 4--6 weeks prior to electropharmacological analysis. Neurones 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 analogues, L-aspartate, DL-homocysteate, N-methyl-D-aspartate, and DL-ibotenate activated two distinct mechanisms of excitation. The primary effect was depolarization accomplished by an apparent decrease of neurone input conductance (Gm). However, in most instances an expected increase in Gm was also observed, especially if membrane potential was reduced by tonic depolarization. Another glutamate analogue, 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 strongly dependent upon 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 favoured the electrogenesis of regenerative potentials that were insensitive to tetrodotoxin. A voltage-dependent increase in sodium and (or) calcium conductance (GNa, GCa) or a decrease in potassium conductance (GK) is suggested to account for this decrease in Gm. Divalent cations (Mg and Co) reduced the depolarizing actions of all amino acids except for those to kainate. The decrease in Gm was more sensitive to Mg than was the increase of Gm. However, the receptor antagonist DL-alpha-aminoadipate blocked both 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.
D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D046508:Culture Techniques; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009431:Neural Conduction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy
D000596:Amino Acids; D005971:Glutamates; D018698:Glutamic Acid; D008274:Magnesium