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Updated: Jul 11, 2026
Mitochondrial Ca2+ Retention Capacity Assay and Ca2+-triggered Mitochondrial Swelling Assay
Published on: May 1, 2018
Spinal cord mitochondria display lower calcium retention capacity compared with brain mitochondria without inherent
Saori Morota1, Magnus J Hansson, Nagao Ishii
1Department of Anesthesiology, Tokyo Medical University Hachioji Medical Center, Tatemachi, Hachioji, Japan.
Abstract:
The mitochondrial permeability transition (mPT) is a potential pathogenic mechanism in neurodegeneration. Varying sensitivity to calcium-induced mPT has been demonstrated for regions within the CNS possibly correlating with vulnerability following insults. The spinal cord is selectively vulnerable in e.g. amyotrophic lateral sclerosis and increased mPT sensitivity of mitochondria derived from the spinal cord has previously been demonstrated. In this study, we introduce whole-body hypothermia prior to removal of CNS tissue to minimize the effects of differential tissue extraction prior to isolation of spinal cord and cortical brain mitochondria. Spinal cord mitochondria were able to retain considerably less calcium when administered as continuous infusion, which was not related to a general increased sensitivity of the mPT to calcium, its desensitization to calcium by the cyclophilin D inhibitor cyclosporin-A, or to differences in respiratory parameters. Spinal cord mitochondria maintained a higher concentration of extramitochondrial calcium during infusion than brain mitochondria possibly related to an increased set-point concentration for calcium uptake. A hampered transport and retention capacity of calcium may translate into an increased susceptibility of the spinal cord to neurodegenerative processes involving calcium-mediated damage.
Insights
Spinal cord mitochondria retain less calcium than brain mitochondria, potentially increasing susceptibility to neurodegeneration. This difference in calcium handling is not due to altered mitochondrial permeability transition (mPT) sensitivity.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Neurodegeneration
Background:
- Mitochondrial permeability transition (mPT) is implicated in neurodegenerative diseases.
- Spinal cord vulnerability in conditions like ALS suggests region-specific differences in mitochondrial function.
- Previous studies indicated heightened mPT sensitivity in spinal cord mitochondria.
Purpose of the Study:
- To investigate calcium handling differences between spinal cord and cortical mitochondria.
- To assess the role of mitochondrial permeability transition (mPT) in these regional differences.
- To understand the impact of hypothermia on mitochondrial calcium retention during tissue extraction.
Main Methods:
- Isolation of spinal cord and cortical mitochondria following whole-body hypothermia.
- Measurement of calcium retention capacity via continuous calcium infusion.
- Assessment of mPT sensitivity using cyclosporin-A.
- Analysis of respiratory parameters and extramitochondrial calcium concentrations.
Main Results:
- Spinal cord mitochondria retained significantly less calcium during continuous infusion compared to brain mitochondria.
- This reduced calcium retention was not linked to increased mPT sensitivity or altered respiratory function.
- Spinal cord mitochondria maintained higher extramitochondrial calcium levels, suggesting a different calcium uptake set-point.
Conclusions:
- Spinal cord mitochondria exhibit distinct calcium transport and retention properties compared to brain mitochondria.
- A hampered calcium handling capacity in spinal cord mitochondria may contribute to its selective vulnerability in neurodegeneration.
- These findings highlight potential calcium-mediated damage mechanisms in spinal cord neurodegenerative processes.
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