PH-DEPENDENT FACILITATION OF SYNAPTIC TRANSMISSION BY HISTAMINE IN THE CA1 REGION OF MOUSE HIPPOCAMPUS

The action of histamine on excitatory synaptic transmission in the CA1 region of the mouse hippocampus was investigated. In a medium at pH 7 .4 population spikes were increased for similar to 60 min after a brie f (5 min) perfusion with histamine (5 mu M) but excitatory postsynapti c potentials (EPSPs) were unaffected, as previously reported in the ra t. At pH 7.0, however, a late component of extra- and intracellularly registered EPSPs was enhanced in two phases: a shorter (by 30%) and a longer lasting one (>1 h by 10%). The NMDA antagonist aminophosphonova lerate (60 mu M) blocked this late component and prevented the EPSP br oadening by histamine. In some cells histamine induced burst-firing an d prolonged EPSPs. The actions on EPSPs were not mediated by any of th e known histamine receptors as they were not mimicked by histamine H1, H2 and H3 agonists or blocked by H1, H2 or H3 antagonists. We conclud e that histamine enhances a late (NMDA) component of hippocampal EPSPs when protonization is increased by a slight shift of the pH in the ac idic direction. Such shifts occur during intense nervous discharges, e .g. in epileptic tissue or following tetanic stimulation, and in hypox ic conditions.