Related Experiment Video
Updated: Aug 15, 2026

Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Manganese and calcium efflux kinetics in brain mitochondria. Relevance to manganese toxicity
C E Gavin1, K K Gunter, T E Gunter
1University of Rochester Medical Center, NY 14642.
Abstract:
Manganese shares the uniport mechanism of mitochondrial calcium influx, accumulates in mitochondria and is cleared only very slowly from brain. Using dual-label isotope techniques, we have investigated both Mn2+ and Ca2+ mitochondrial efflux kinetics. We report that (1) there is no significant Na(+)-dependent Mn2+ efflux from brain mitochondria; (2) Mn2+ inhibits both Na(+)-dependent and Na(+)-independent Ca2+ efflux in brain, in a mode that appears to be primarily competitive and with apparent Ki values of 5.1 and 7.9 nmol/mg respectively; and (3) Ca2+ does not appear to inhibit Mn2+ efflux from brain mitochondria. Findings (1) and (2) suggest the possibility of mitochondrial accumulation of both Mn2+ and Ca2+ in Mn2(+)-intoxicated brain.
Insights
Manganese (Mn2+) accumulates in brain mitochondria and hinders calcium (Ca2+) removal. This study shows Mn2+ blocks Ca2+ efflux, suggesting potential co-accumulation during manganese intoxication.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Toxicology
Background:
- Manganese (Mn2+) influx into mitochondria shares a mechanism with calcium (Ca2+).
- Manganese accumulates in brain mitochondria and is slowly cleared.
- Understanding manganese and calcium efflux is crucial for neurotoxicity research.
Purpose of the Study:
- To investigate the mitochondrial efflux kinetics of both Mn2+ and Ca2+ in the brain.
- To determine the role of Na+ in Mn2+ and Ca2+ efflux.
- To explore the competitive interactions between Mn2+ and Ca2+ in mitochondrial efflux.
Main Methods:
- Utilized dual-label isotope techniques to track Mn2+ and Ca2+ efflux.
- Examined Na+-dependent and Na+-independent efflux pathways.
- Assessed the inhibitory effects of Mn2+ on Ca2+ efflux and vice versa.
Main Results:
- No significant Na+-dependent Mn2+ efflux was observed from brain mitochondria.
- Mn2+ competitively inhibited both Na+-dependent and Na+-independent Ca2+ efflux.
- Ca2+ did not significantly inhibit Mn2+ efflux from brain mitochondria.
Conclusions:
- Manganese (Mn2+) efflux from brain mitochondria is primarily Na+-independent.
- Manganese significantly inhibits calcium (Ca2+) efflux, suggesting competitive interaction.
- Findings indicate a potential for mitochondrial co-accumulation of Mn2+ and Ca2+ in manganese-intoxicated brain tissue.
Related Concept Videos
The Significance of Membrane Transport
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Mitochondrial Membranes
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...

