pH dependence of histamine modulation on NMDA response in hippocampal slices

Abstract

The histaminergic system in the brain emanates from the tuberomammilary nucleusof the posterior hypothalamus and projects to the whole central nervous system. In thisresearch, the effect of histamine was investigated in the CAl region of the hippocampusof rats in vitro. The enhancement of activity mediated by classical histamine receptors hasbeen confirmed and a new independent action of histamine on N-Methyl D-Aspartaticacid (NMDA) receptors has been described in,1. hippocampal slices as an epileptiform field activity in magnesium free medium,representing NMDA receptor mediated extracellular activity ,2. thin hippocampal slices with patch-clamp technique as an effect on the NMDAcomponents of excitatory postsynaptic currents.The extracellular activity evoked by the stimulation of Schaffer collateralcommisuralpathway was recorded from CA I stratum pyramidale and stratum radiatumThe NMDA components of excitatory currents evoked by glutamate in the CAl regionof rat hippocampal slices and their modification by histamine were investigated by usingthe patch-clamp tight seal whole cell recording technique. In this study it has been foundthat histamine has no influence on non-NMDA current but effects the NMDA current ina pH dependent way. Histamine potentiates the NMDA current at pH 7.2 while itdepresses the current at pH 7.6. The NMDA current modification by histamine was notmediated by the activation of known histamine receptors of HI, H2 or H3 type. Theeffect resembles the known interaction of polyamines with the NMDA receptorionophorecomplex. This work is consistent with the concentration clamp experiments inisolated hippocampal pyramidal cells and emphasizes the physiological andpathophysiological implications: Slight shifts in pH as shown here to profoundlyinfluence the histamine action occur locally during intense nervous activity, tetanicstimulation and globally during anoxia. The modulating action of the histaminergicsystem in the brain will be specifically targetted towards plasticity under these conditions.Keywords:Histamine modulation, NMDA receptors, Patch-clamp technique, pH.