Relevance to manganese toxicity

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 K1 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.