Methylmercury Alters Intrasynaptosomal Concentrations of Endogenous Polyvalent Cations

Denny, Michael F.; Hare, Michael F.; Atchison, William D.

doi:10.1006/taap.1993.1191

Cited by 50 publications

(29 citation statements)

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“…The contribution of more than one intracellular store agrees with results of experiments in T lymphocytes, in which MeHg caused release of Ca 2ϩ from both mitochondria and SER (Tan et al, 1993). However, the first-phase increase in fura-2 ratio is not comprised solely of Ca 2ϩ , because there is at least one other divalent cation whose intracellular levels increase in response to MeHg (Denny et al, 1993;Hare et al, 1993;Marty and Atchison, 1997). In rat cortical synaptosomes, this cation was identified as Zn 2ϩ by 19 F-NMR (Denny and Atchison, 1994).…”

Section: Discussionsupporting

confidence: 77%

Evidence for Interactions between Intracellular Calcium Stores during Methylmercury-Induced Intracellular Calcium Dysregulation in Rat Cerebellar Granule Neurons

Limke¹,

Otero-Montañez²,

Atchison³

2003

J Pharmacol Exp Ther

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ABSTRACTand was abolished by mitochondrial depolarization. The secondary increase was associated with spreading of the dye from punctate staining to whole-cell distribution, and was delayed significantly by the MTP inhibitor cyclosporin A and the smooth endoplasmic reticulum Ca 2ϩ ATPase inhibitor thapsigargin. We conclude that MeHg causes release of Ca 2ϩ from the mitochondria through opening of the MTP, which contributes the bulk of the elevated [Ca 2ϩ ] i observed during MeHg neurotoxicity. Additionally, the Ca 2ϩ that enters the mitochondria seems to originate in the smooth endoplasmic reticulum, providing a mechanism for the observed mitochondrial Ca 2ϩ overload.

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Section: Discussionsupporting

confidence: 77%

Evidence for Interactions between Intracellular Calcium Stores during Methylmercury-Induced Intracellular Calcium Dysregulation in Rat Cerebellar Granule Neurons

Limke¹,

Otero-Montañez²,

Atchison³

2003

J Pharmacol Exp Ther

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“…In hippocampal CA1 neurons, EPSPs or EPSCs were evoked by subthreshold stimulation of Schaffer collaterals, axons of CA3 pyramidal cells, whereas the recurrent IPSPs or IPSCs were evoked by subthreshold antidromic stimulation of the alveus to activate the interneurons Atchison, 1995, 1997 Hare and Atchison, 1995), and cerebellar granule and Purkinje cells in culture (Marty and Atchison, , 1998Limke and Atchison, 2002;Limke et al, 2003;Edwards et al, 2005). MeHg-induced elevations of [Ca 2ϩ ] i were also observed in rat brain synaptosomes (Komulainen and Bondy, 1987;Kauppinen et al, 1989; molpharm.aspetjournals.org Denny et al, 1993) and non-neuronal cell such as T-lymphocytes (Tan et al, 1993). Thus, this effect too seems to be universal.…”

Section: Differential Effects Of Mehg On Glutamatergic Andmentioning

confidence: 97%

Methylmercury-Induced Increase of Intracellular Ca²⁺ Increases Spontaneous Synaptic Current Frequency in Rat Cerebellar Slices

Yuan

Atchison

2007

Mol Pharmacol

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The relationship between increased intracellular calcium concentration ([Ca 2ϩ ] i ) and changes in spontaneous synaptic current frequency caused by the neurotoxicant methylmercury (MeHg) was examined in Purkinje cells of cerebellar slices using confocal microscopy and whole-cell recording. MeHg (10 -100 M) stimulated and then suppressed completely the frequency of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs). Current amplitude was also initially in-

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“…MeHg also causes an increase in intracellular Zn 2ϩ , an ion that is able to permeate a number of cation channels (Denny et al, 1993;Denny and Atchison, 1994). The divalent cation Zn 2ϩ is present throughout the mammalian CNS and concentrated in nerve terminals.…”

Section: Mehg-induced Giant Slow Inward Currents Are Not Mediated By mentioning

confidence: 99%

“…Several types of smooth muscle cells (Hashitani and Edwards, 1999;Toland et al, 2000;Sergeant et al, 2001) influx or/and intracellular store Ca 2ϩ release in a variety of cell types (Denny et al, 1993;Hare et al, 1993;Sarafian, 1993). It is possible that an increase in [Ca 2ϩ ] i induces current flow through Ca 2ϩ -activated Cl Ϫ channels, which in turn generates the giant slow inward currents.…”

Section: Mehg-induced Giant Slow Inward Currents Are Not Mediated By mentioning

confidence: 99%

Methylmercury Induces a Spontaneous, Transient Slow Inward Chloride Current in Purkinje Cells of Rat Cerebellar Slices

Yuan

Atchison

2005

J Pharmacol Exp Ther

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Methylmercury (MeHg; 10 -100 M) induced a spontaneous, transient, slow inward current in Purkinje cells in rat cerebellar slices. Insensitivity of this current to tetrodotoxin suggests that its generation is not related to presynaptic firing. The present study was designed to attempt to identify the ionic origin of this current. Neither Gd 3ϩ , a nonspecific cation channel blocker, nor tetrakis(2-pyridylmethyl)ethylethylenediamine, which chelates Zn 2ϩ , could prevent this current. Following dialysis of cells with a low-[Cl Ϫ ] pipette solution, the giant currents were inducible only when the cells were held at potentials more positive than 0 mV but not at potentials more negative than Ϫ60 mV. In addition, no giant currents were observed when cells were held at 0 mV under symmetrical [Cl Ϫ ] conditions. Thus, this current seems to be mediated by Cl Ϫ . However, it was insensitive to the glycine receptor antagonist strychnine. The anion channel blockers 4,4Ј-diisothiocyanostilbene-2,2Ј-disulfonic acid (DIDS) or niflumic acid suppressed GABA A receptor-mediated spontaneous inhibitory postsynaptic currents. Niflumic acid also prevented appearance of this giant current; DIDS was only effective at more positive membrane potentials. Thus, this current seems to be carried by a voltage-dependent Cl Ϫ

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Methylmercury Alters Intrasynaptosomal Concentrations of Endogenous Polyvalent Cations

Cited by 50 publications

References 0 publications

Evidence for Interactions between Intracellular Calcium Stores during Methylmercury-Induced Intracellular Calcium Dysregulation in Rat Cerebellar Granule Neurons

Evidence for Interactions between Intracellular Calcium Stores during Methylmercury-Induced Intracellular Calcium Dysregulation in Rat Cerebellar Granule Neurons

Methylmercury-Induced Increase of Intracellular Ca²⁺ Increases Spontaneous Synaptic Current Frequency in Rat Cerebellar Slices

Methylmercury Induces a Spontaneous, Transient Slow Inward Chloride Current in Purkinje Cells of Rat Cerebellar Slices

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Methylmercury Alters Intrasynaptosomal Concentrations of Endogenous Polyvalent Cations

Cited by 50 publications

References 0 publications

Evidence for Interactions between Intracellular Calcium Stores during Methylmercury-Induced Intracellular Calcium Dysregulation in Rat Cerebellar Granule Neurons

Evidence for Interactions between Intracellular Calcium Stores during Methylmercury-Induced Intracellular Calcium Dysregulation in Rat Cerebellar Granule Neurons

Methylmercury-Induced Increase of Intracellular Ca2+ Increases Spontaneous Synaptic Current Frequency in Rat Cerebellar Slices

Methylmercury Induces a Spontaneous, Transient Slow Inward Chloride Current in Purkinje Cells of Rat Cerebellar Slices

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Methylmercury-Induced Increase of Intracellular Ca²⁺ Increases Spontaneous Synaptic Current Frequency in Rat Cerebellar Slices