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 3H-AMPA ([3H]-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 ([3H]-6-cyano-7-nitroquinoxaline-2,3-dione; 3H-CNQX) to AMPA receptors in slices expressing KCl-induced LTP. Administration of the phospholipase A2 (PLA2) inhibitor bromophenacyl bromide (BPB) prior to potassium application prevented LTP formation as well as the changes in paired-pulse facilitation and 3H-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 PLA2 activation is an important mechanism in long-term changes of synaptic operation.