NMDA and quisqualate reduce a Ca-dependent K+ current by a protein kinase-mediated mechanism.
Stimulation of N-methyl-D-aspartate (NMDA) or quisqualate (Quis) receptors by submicromolar concentrations of NMDA or Quis but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) reduced post-spike train after hyperpolarizations (AHPs) and blocked the underlying Iahp in dentate granule (DG) neurones in vitro. The NMDA but not Quis action was blocked by the NMDA receptor blocker 2-D,L-aminophosphonovaleric acid (APV). Actions of both NMDA and Quis were abolished by isoquinolinesulphonyl-2-methyl-piperazine dihydrochloride (H-7), an inhibitor of several protein kinases. These data suggest that there is a link between excitatory amino acid receptor activation, the protein kinase system, and neuronal excitability.
Baskys
A
A
Playfair Neuroscience Unit, Toronto Western Hospital, Canada.
Bernstein
N K
NK
Barolet
A W
AW
Carlen
P L
PL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D016318:Quisqualic Acid; D051381:Rats; D011916:Rats, Inbred F344; D015290:Second Messenger Systems
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010069:Oxadiazoles; D010879:Piperazines; D001224:Aspartic Acid; D016202:N-Methylaspartate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016318:Quisqualic Acid; D011494:Protein Kinases; D011188:Potassium; D002118:Calcium