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08:48
Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models
Published on: June 30, 2023
Mitochondrial dysfunction is involved in P2X7 receptor-mediated neuronal cell death
Kentaro Nishida1, Tsunetoshi Nakatani, Akihiro Ohishi
1Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
Journal of Neurochemistry
|July 11, 2012
Summary
The P2X7 receptor (P2X7R) is functionally expressed in neurons and contributes to ATP-induced neuronal death. P2X7R activation triggers calcium influx and mitochondrial dysfunction, leading to apoptosis in cortical neurons.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- The P2X7 receptor (P2X7R) is recognized as a 'death receptor' in immune cells.
- Its functional expression and role in non-immune cells, particularly neurons, remain debated.
Purpose of the Study:
- To investigate the involvement of P2X7R activation and mitochondrial dysfunction in ATP-induced neuronal death.
- To determine the role of P2X7R in cultured cortical neurons.
Main Methods:
- Utilized cultured cortical neurons expressing P2X7R and pannexin-1.
- Administered ATP or BzATP and assessed neuronal death, apoptosis, Ca(2+) entry, YO-PRO-1 uptake, and mitochondrial function.
- Employed P2X7R antagonists (oxATP, A438079), pannexin-1 blockers (carbenoxolone), caspase inhibitors, and calpain inhibitors.
Main Results:
- ATP or BzATP induced neuronal death, including apoptosis, which was prevented by P2X7R antagonists.
- P2X7R activation led to Ca(2+) influx and mitochondrial dysfunction, evidenced by increased Rhodamine123 efflux.
- Inhibition of P2X7R, but not pannexin-1, prevented ATP-induced neuronal death.
- Mitochondrial dysfunction and subsequent caspase and calpain activation contributed to neuronal death.
Conclusions:
- P2X7R is functionally expressed in cultured cortical neurons.
- P2X7R activation triggers Ca(2+) entry and mitochondrial dysfunction, playing critical roles in ATP-induced neuronal death.
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