Giant depolarizing potentials (GDPs) are generated by the interplay of the depolarizing action of GABA and glutamate. In this study, single and dual whole cell recordings (in current-clamp configuration) were performed from CA3 pyramidal cells in hippocampal slices obtained from postnatal (P) days P1- to P6-old rats to evaluate the role of ionotropic glutamate receptors in GDP generation. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-40 μM) completely blocked GDPs. However, in the presence of CNQX, it was still possible to re-induce the appearance of GDPs with GABA (20 μM) or (RS)-α-amino-3-hydroxy-5-methyl-4-isoxadepropionate (AMPA) (5 μM). This effect was prevented by the more potent and selective AMPA receptor antagonist GYKI 53655 (50-100 μM). In the presence of GYKI 53655, both kainic or domoic acid (0.1-1 μM) were unable to induce GDPs. In contrast, bath application of D-(-)-2-amino-5-phosphonopentanoic acid (50 μM) or (+)- 3-(2-carboxy-piperazin-4-yl)-propyl-L-phosphonic acid (20 μM) produced only a 37 ± 9% (SE) and 36 ± 11% reduction in GDPs frequency, respectively. Cyclothiazide, a selective blocker of AMPA receptor desensitization, increased GDP frequency by 76 ± 14%. Experiments were also performed with an intracellular solution containing KF to block GABA(A) receptor-mediated responses. In these conditions, a glutamatergic component of GDP was revealed. GDPs could still be recorded synchronous with those detected simultaneously with KCl-filled electrodes, although their amplitude was smaller. Similar results were found in pair recordings obtained from minislices containing only a small portion of the CA3 area. These data suggest that GDP generation requires activation of AMPA receptors by local release of glutamate from recurrent collaterals.
|Number of pages||8|
|Journal||Journal of Neurophysiology|
|Publication status||Published - 1999|
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