Pregnenolone sulfate (PS), an endogenously occurring neurosteroid, has been shown to modulate the activity of several neurotransmitter-gated channels, including the NMDA receptor (NMDAR). NMDARs are glutamate-gated ion channels involved in excitatory synaptic transmission, synaptic plasticity, and excitotoxicity. In this study, we analyzed the effects of PS on calcium signaling in cultured hippocampal neurons and HEK293 cells expressing NMDAR. The cells were loaded with the Ca(2+) sensor Fura-2. In agreement with previous electrophysiological experiments, PS potentiated the increases in intracellular Ca(2+) induced by an exogenous application of glutamate; however, PS also increased intracellular Ca(2+) in the absence of exogenous NMDA agonist. The agonist-independent effect of PS was induced in all neurons studied and in HEK293 cells expressing GluN1/GluN2A-B receptors in a neurosteroid-specific manner. We conclude that PS is an endogenous NMDA agonist that activates the GluN1/GluN2A-B receptors.
- MeSH
- gating iontového kanálu fyziologie MeSH
- HEK293 buňky MeSH
- lidé MeSH
- pregnenolon metabolismus MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- vápník metabolismus MeSH
- vápníková signalizace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH