1. In acutely isolated hippocampal cells, NMDA and glutamate application suppressed GABAA receptor-mediated responses. We studied the cellular events underlying the interaction between the two classes of receptors by using a whole-cell voltage-clamp approach. 2. Following an NMDA application, an outward current mediated by GABAA receptor activation (GABA response) was suppressed for up to 12 s. The suppression of the GABA response was reduced when Ca2+ in the extracellular solution was replaced by Ba2+ or when intracellular BAPTA (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)was increased from 1 to 10 mM. 3. Replacing ATP in the intracellular solution by adenosine-5'-0-3-thiotriphosphate reduced the suppressive effect of NMDA application on the GABA response. Okadaic acid, a phosphatase inhibitor, also prevented the NMDA-induced suppression of the GABA response. In addition, when the intracellular perfusing solution contained the calcineurin autoinhibitory fragment (50 /1M), suppression of the GABA response by the NMDA current was also reduced.

1. Ca2+ current was examined in acutely isolated hippocampal cells with the use of whole cell voltage-clamp recording and under continuous intracellular perfusion. A persistent Ca2+ current was activated by depolarization to -10 mV from a holding potential of -50 mV. 2. The persistent Ca2+ current was suppressed upon a wash out of the intracellular Mg(2+)-ATP. Adenosine 3',5'-cyclic monophosphate (cAMP) introduced intracellularly potentiated the Ca2+ current, and kinase A inhibitor blocked the current. 3. Reversible suppression of the persistent Ca2+ current was also observed by elevating intracellular Ca2+. This Ca(2+)-dependent suppression was retarded by the addition of a phosphatase inhibitor, okadaic acid, to the intracellular solution. 4. N-methyl-D-aspartate (NMDA) elicited inward current (NMDA response) in the isolated cells. The persistent Ca2+ current was transiently suppressed after the NMDA response. Suppression of the Ca2+ current by NMDA was reduced when intracellular Ca2+ buffering capacity was increased by increasing the concentration of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) from a concentration of 1-10 mM. 5. Substitution of ATP in the intracellular solution with ATP-gamma-S or the addition of okadaic acid to the intracellular solution reduced the suppressive effect of NMDA on the Ca2+ current. 6. The results suggest that the persistent Ca2+ current in the hippocampal cells is maintained by a kinase A-mediated phosphorylation. Increases in the intracellular Ca2+ concentration suppressed the Ca2+ current via a mechanism involving a phosphatase. Ca2+ entry through the NMDA receptor channel suppressed the Ca2+ channel by activating the phosphatase.