Ca2+-dependent depolarization and burst firing of rat CA1 pyramidal neurones induced by N-methyl-D-aspartic acid and quinolinic acid: antagonism by 2-amino-5-phosphonovaleric and kynurenic acids

Abstract

The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-1-D-aspartic (NMDA), and quinolinic (QUIN) acids were investigated using intracellular recording from CA1 pyramidal neurones in slices of rat hippocampus. QUIS evoked only simple action potentials superimposed upon a depolarization which attained a clear plateau. When this level had been reached, increased ejecting currents did not produce further depolarization. By contrast, with low currents NMDA and QUIN elicited small membrane depolarizations which triggered burst of action potentials superimposed upon rhythmically occurring depolarizing shifts. Larger currents caused depolarization which is sufficiently large completely blocked spike activity. Tetrodotoxin (TTX) prevented the spikes evoked by QUIS and the burst of action potentials seen with NMDA and QUIN, and the rhythmic depolarizing shifts then appeared as broad spikes of up to 50 mV in amplitude. These and the underlying membrane depolarization were blocked by Co2+, by the NMDA antagonist D(-)-2-amino-5-phosphonovaleric acid (DAPV), and by kynurenic acid (KYNU). It thus appears that the depolarization and burst firing of rat CA1 pyramidal neurones elicited by NMDA and QUIN and Ca2+ dependent while the actions of QUIS are not.