G-protein modulation of glycine-resistant NMDA receptor desensitization in rat cultured hippocampal neurons.
Activation of N-methyl-D-aspartate (NMDA) subtype glutamate receptors increases the excitability of most neurons within the CNS. A common feature of ionotropic glutamate receptors is their ability to undergo desensitization. In the present experiments we have examined the role of guanine nucleotide-binding proteins (G-proteins) in the regulation of NMDA receptor desensitization. Repeated NMDA receptor activation with 2 mM extracellular Ca2+ increased the degree of glycine-resistant NMDA receptor desensitization of subsequent responses to NMDA recorded in the presence of 0.2 mM Ca2+. The recovery of glycine-resistant NMDA receptor desensitization after repeated NMDA receptor activation in the presence of 2 mM Ca2+ was significantly reduced in neurons intracellularly dialysed with guanosine-5'-O-(3-thiotriphosphate), guanosine-5'-triphosphate or AlCl3 and CsF, compounds known to activate G-proteins. Intracellular dialysis with guanosine-5'-O-(2-thiodiphosphate), adenosine triphosphate, adenosine triphosphate, or adenosine-5'-O-(3-thiotriphosphate) was ineffective. The calcium permeability of NMDA receptor-channels was not altered by intracellular dialysis with GTP gamma S. This suggests that modulation of NMDA receptor desensitization by G-proteins represents a novel mechanism for regulation of glutamate-gated ion channel activity.
Turecek
R
R
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Vyklický
L
L
Vlachová
V
V
Vyklický
L
L
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D005998:Glycine / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D002118:Calcium; D005998:Glycine