Actions of phosphomonoesters on CA1 hippocampal neurons as revealed by a combined electrophysiological and nuclear magnetic resonance study

Abstract

Phosphomonoesters (PMEs), precursors of membrane phospholipids, are found in high levels in the developing brain and Alzheimer's disease brain. The present study details the neurophysiological and metabolic effects of acute PME elevation on the Fisher 344 rat in vitro hippocampal slice. Two abundant PMEs, phosphoethanolamine (PE) and L-phosphoserine (PS), reliably altered properties of synaptic transmission at the Schaffer collateral/commissural-CA1 cell synapse. Specifically, PE reversibly depressed the amplitude of population EPSPs at millimolar concentrations but had no effect at micromolar concentrations. PS had biphasic effects on population EPSPs, inducing first a reduction followed by an enhancement of response amplitude. In contrast to PE, the effects of PS were not reversible; population EPSPs were augmented during the wash of PS, and the CA3 region generated evoked (but not spontaneous) epileptiform discharges. 31P nuclear magnetic resonance spectroscopy revealed enhanced slice uptake of PS compared to PE. There was no significant effect of PE on slice high-energy phosphates but incubation with PS significantly lowered slice phosphocreatine (PCr) and ATP concentrations. These observations indicate that the slice uptake of PS could be energy requiring and the enhanced response amplitude observed at 5 mM PS also could produce a drain on high-energy phosphates. Possible modes of PME action on hippocampal physiology are discussed.