Platelet-activating factor inhibits ionotropic GABA receptor activity in cultured hippocampal neurons.
Platelet-activating factor (PAF), one of the most potent bioactive lipids, has been implicated in modulating long-term potentiation (LTP) and neurotoxicity. In the CNS, glutamate and GABA are the major excitatory and inhibitory neurotransmitters, respectively. Previous work has focused on the effects of PAF on glutamatergic receptor responses. The purpose of the present study was to investigate the possible actions of PAF on ionotropic GABA receptor responses in primary cultured hippocampal neurons using the whole-cell and single channel patch clamp techniques. Extracellular application of PAF induced a reduction of the GABA gated Cl- current in a majority of cells (29 of 44 cells), while it caused an enhancement in 10 of 44 cells. A similar heterogeneous modulation of PAF on the GABA receptor activities was also observed in outside-out patch recordings. Moreover, the cell-attached single channel recordings showed that PAF decreased the GABA channel activity. Therefore, PAF may modulate synaptic activity by inhibiting GABA receptor channels. During seizures and neural injury, when enhanced synthesis of this lipid mediator takes place, the actions of PAF on inhibitory GABA receptors may contribute to synaptic dysfunction.
Chen
C
C
Neuroscience Center, Louisiana State University Medical Center, New Orleans 70112, USA.
Bazan
N G
NG
D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D002712:Chlorides; D018756:GABA Antagonists; D007473:Ion Channels; D010972:Platelet Activating Factor; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid