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Abstract

Disruption of brain mitochondrial calcium sequestration by methylmercury.

P C Levesque and W D Atchison
Journal of Pharmacology and Experimental Therapeutics January 1991, 256 (1) 236-242;
P C Levesque
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W D Atchison
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Abstract

In vitro effects of methylmercury (MeHg) on Ca2+ transport and respiratory control of mitochondria isolated from rat forebrain were examined to determine whether MeHg disrupted sequestration of Ca2+ by neuronal mitochondria. Uptake of 45Ca2+ by mitochondria and release of 45Ca2+ from preloaded mitochondria were measured in the presence and absence of ATP. Release of 45Ca2+ from preloaded mitochondria by MeHg was measured in the presence and absence of ruthenium red (RR), a putative inhibitor of the mitochondrial Ca2+ uptake uniporter. During incubation intervals ranging from 10 sec to 5 min, 10 microM MeHg reduced mitochondrial uptake of 45Ca2+ by about 50% and 100 microM MeHg completely prevented 45Ca2+ uptake. These effects of MeHg occurred in both the presence and absence of ATP. Exposure of mitochondria preloaded with 45Ca2+ to either 10 microM or 100 microM MeHg for 10 sec resulted in increased efflux of 45Ca2+ of 10% and 65%, respectively, in both the absence and presence of ATP. Loading mitochondria with 45Ca2+ in the presence of 20 microM RR reduced total uptake of 45Ca2+ and greatly attenuated MeHg-induced release of 45Ca2+ from mitochondria. RR did not inhibit the effects of MeHg on Ca2+ release by merely preventing the binding of MeHg to mitochondria because RR did not alter mitochondrial binding of methyl[203Hg]. The ratio of state 3 to state 4 respiration (respiratory control ratio) was measured as a means of assessing functional integrity of isolated mitochondria in the absence and presence of MeHg. Control ratios of from 3 to 5 were only marginally reduced by 2 microM MeHg but were greatly reduced by 10 and 20 microM MeHg.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 256, Issue 1
1 Jan 1991
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Abstract

Disruption of brain mitochondrial calcium sequestration by methylmercury.

P C Levesque and W D Atchison
Journal of Pharmacology and Experimental Therapeutics January 1, 1991, 256 (1) 236-242;

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Abstract

Disruption of brain mitochondrial calcium sequestration by methylmercury.

P C Levesque and W D Atchison
Journal of Pharmacology and Experimental Therapeutics January 1, 1991, 256 (1) 236-242;
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