Regulation of Ca2+ transport in brain mitochondria. I. The mechanism of spermine enhancement of Ca2+ uptake and retention
Abstract
Spermine enhances electrogenic Ca2+ uptake and inhibits Na(+)-independent Ca2+ efflux in rat brain mitochondria. As a result, Ca2+ retention by brain mitochondria increases greatly and the external free Ca2+ level at steady-state can be lowered to physiologically relevant concentrations. The stimulation of Ca2+ uptake by spermine is more pronounced at low concentrations of Ca2+, effectively lowering the apparent Km for Ca2+ uptake from 3 microM to 1.5 microM. However, the apparent Vmax is also increased. At low Ca2+ concentrations, Ca2+ uptake is diffusion-limited. Spermine strongly inhibits Ca2+ binding to anionic phospholipids and it is suggested that this increases the rate of surface diffusion which reduces the apparent Km for uptake. The same effect could inhibit the Na(+)-independent efflux if the rate of efflux is limited by Ca2+ dissociation from the efflux carrier. In brain mitochondria (but not in liver) the spermine effect depends on the presence of ADP. In a medium that contains physiological concentrations of Pi, Mg+, K+, ADP and spermine, brain mitochondria sequester Ca2+ down to 0.1 microM and below, depending on the matrix Ca2+ load. Moreover, brain mitochondria under the same conditions buffer the external medium at 0.4 microM, a concentration at which the set point becomes independent of the matrix Ca2+ content. Thus, mitochondria appear to be capable of modulating calcium oscillations in brain cells.
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Spermine and other polyamines inhibit mPTP in isolated mitochondria.
“since spermine and other polyamines have been shown to inhibit mPTP in isolated mitochondria [280,281,282].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [280]
Spermidine likely has a direct effect on mPTP.
“Therefore, it is more than likely that there is also a direct effect of spermidine on mPTP”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [280]
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- Authors
- Rottenberg, H., & Marbach, M.
- Affiliations
- Hahnemann University Hospital (US)
- Corresponding author
- Rottenberg, Hagai
- ORCID
- Rottenberg, Hagai
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 1990-03
- Volume
- 1016
- Issue
- 1
- Pages
- 77-86
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W1981967527
- Cited by
- 60
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 2
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AAO7238)
- National Institute of General Medical Sciences (GM 28173)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- calcium transport, brain mitochondria, spermine, calcium uptake, calcium retention, ADP, calcium buffering, calcium oscillations
- MeSH terms
- Animals, Biological Transport, Brain, Calcium, Kinetics, Male, Mitochondria, Models, Chemical, Rats, Inbred Strains, Spermine, Rats, In Vitro Techniques
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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