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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) reduced post-spike train afterhyperpolarizations (AHPs) and blocked the underlying Iaph 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 isoquino-linesulphonyl-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. © 1990.