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Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics.
Brain Res 2006; 1113(1):210-9BR

Abstract

The neurotoxicity of manganese [Mn] is due in part to glutamate excitotoxicity. Release of ATP by astrocytes is a critical modulator of glutamatergic neurotransmission, which is regulated by calcium (Ca(2+)) waves that propagate through astrocytic networks in response to synaptic activity. It was postulated that Mn alters ATP-dependent intracellular Ca(2+) dynamics in astrocytes, thereby suppressing Ca(2+) wave activity. Confluent primary cultures of cortical astrocytes were loaded with the Ca(2+)-sensitive dye fluo-4 and examined by fluorescence microscopy for Ca(2+) wave activity following micropipet mechanical stimulation of a single cell. Mitochondrial Ca(2+) was evaluated by fluorescence microscopy following addition of ATP using the mitochondrial-specific Ca(2+) dye rhod-2-AM. Imaging studies revealed that pretreatment of astrocytes with 1-10 microM Mn significantly reduced the rate, area, and amplitude of mechanically induced Ca(2+) waves. This attenuation was not a result of inhibited mitochondrial calcium uptake because robust calcium waves were still observed following pretreatment of astrocytes with Ru360, an inhibitor of mitochondrial Ca(2+) uptake, either in coupling or uncoupling conditions. However, determination of endoplasmic reticulum (ER) Ca(2+) levels in cells using the sarco/endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin indicated that Mn reduced the available pool of releasable ER Ca(2+) at concentrations as low as 1 muM. Examination of ATP-stimulated changes in mitochondrial Ca(2+) indicated that, in cells pretreated with Mn, mitochondria retained high levels of Ca(2+). It is concluded that exposure of astrocytes to low concentrations of Mn(2+) results in sequestration of Ca(2+) within the mitochondria that reduces the available pool of releasable Ca(2+) within the ER, thereby inhibiting calcium wave activity.

Authors+Show Affiliations

Molecular, Cellular, and Integrative Neuroscience, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, USA. Ron.Tjalkens@colostate.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16934782

Citation

Tjalkens, Ronald B., et al. "Manganese Suppresses ATP-dependent Intercellular Calcium Waves in Astrocyte Networks Through Alteration of Mitochondrial and Endoplasmic Reticulum Calcium Dynamics." Brain Research, vol. 1113, no. 1, 2006, pp. 210-9.
Tjalkens RB, Zoran MJ, Mohl B, et al. Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics. Brain Res. 2006;1113(1):210-9.
Tjalkens, R. B., Zoran, M. J., Mohl, B., & Barhoumi, R. (2006). Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics. Brain Research, 1113(1), pp. 210-9.
Tjalkens RB, et al. Manganese Suppresses ATP-dependent Intercellular Calcium Waves in Astrocyte Networks Through Alteration of Mitochondrial and Endoplasmic Reticulum Calcium Dynamics. Brain Res. 2006 Oct 3;1113(1):210-9. PubMed PMID: 16934782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics. AU - Tjalkens,Ronald B, AU - Zoran,Mark J, AU - Mohl,Brianne, AU - Barhoumi,Roula, Y1 - 2006/08/28/ PY - 2006/05/02/received PY - 2006/07/11/revised PY - 2006/07/12/accepted PY - 2006/8/29/pubmed PY - 2006/12/14/medline PY - 2006/8/29/entrez SP - 210 EP - 9 JF - Brain research JO - Brain Res. VL - 1113 IS - 1 N2 - The neurotoxicity of manganese [Mn] is due in part to glutamate excitotoxicity. Release of ATP by astrocytes is a critical modulator of glutamatergic neurotransmission, which is regulated by calcium (Ca(2+)) waves that propagate through astrocytic networks in response to synaptic activity. It was postulated that Mn alters ATP-dependent intracellular Ca(2+) dynamics in astrocytes, thereby suppressing Ca(2+) wave activity. Confluent primary cultures of cortical astrocytes were loaded with the Ca(2+)-sensitive dye fluo-4 and examined by fluorescence microscopy for Ca(2+) wave activity following micropipet mechanical stimulation of a single cell. Mitochondrial Ca(2+) was evaluated by fluorescence microscopy following addition of ATP using the mitochondrial-specific Ca(2+) dye rhod-2-AM. Imaging studies revealed that pretreatment of astrocytes with 1-10 microM Mn significantly reduced the rate, area, and amplitude of mechanically induced Ca(2+) waves. This attenuation was not a result of inhibited mitochondrial calcium uptake because robust calcium waves were still observed following pretreatment of astrocytes with Ru360, an inhibitor of mitochondrial Ca(2+) uptake, either in coupling or uncoupling conditions. However, determination of endoplasmic reticulum (ER) Ca(2+) levels in cells using the sarco/endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin indicated that Mn reduced the available pool of releasable ER Ca(2+) at concentrations as low as 1 muM. Examination of ATP-stimulated changes in mitochondrial Ca(2+) indicated that, in cells pretreated with Mn, mitochondria retained high levels of Ca(2+). It is concluded that exposure of astrocytes to low concentrations of Mn(2+) results in sequestration of Ca(2+) within the mitochondria that reduces the available pool of releasable Ca(2+) within the ER, thereby inhibiting calcium wave activity. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/16934782/Manganese_suppresses_ATP_dependent_intercellular_calcium_waves_in_astrocyte_networks_through_alteration_of_mitochondrial_and_endoplasmic_reticulum_calcium_dynamics_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)02136-6 DB - PRIME DP - Unbound Medicine ER -