POTASSIUM-INDUCED LONG-TERM POTENTIATION IN AREA CA1 OF THE HIPPOCAMPUS INVOLVES PHOSPHOLIPASE ACTIVATION

Previous studies have shown that potassium-induced long-term potentiation (LTP) of the Schaffer collateral/commissural synapses in area CA1 of the hippocampus shares common properties with tetanus-induced LTP. In the present investigation, we performed electrophysiological and binding experiments on CA1 hippocampal slices to evaluate the location and nature of the changes underlying potassium-induced LTP. Paired-pulse facilitation, which represents an index of transmitter release, was markedly reduced by potassium-induced LTP. In addition, KCl-induced LTP was associated with an increase in H-3-AMPA ([H-3]-amino-3-hydroxy-5-methylisoxazole-4-propionate) binding to CA1 synaptic membranes when measured 40 min after high-potassium exposure; however, no changes were detected in binding of an antagonist ([H-3]-6-cyano-7-nitroquinoxaline-2,3-dione; H-3-CNQX) to AMPA receptors in slices expressing KCI-induced LTP. Administration of the phospholipase A(2) (PLA(2)) inhibitor bromophenacyl bromide (BPB) prior to potassium application prevented LTP formation as well as the changes in paired-pulse facilitation and H-3-AMPA binding that characterized this type of potentiation. Taken together, these data indicate that potassium-induced LTP may be related to modifications in both pre- and postsynaptic properties and confirm the hypothesis that PLA(2) activation is an important mechanism in long-term changes of synaptic operation. (c) 1994 Wiley-Liss, Inc.