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Anion channels modulate store-operated calcium influx in human microglia.
Cell Calcium. 2000 Oct; 28(4):261-8.CC

Abstract

Recent work from this laboratory has demonstrated that purinergic-mediated depolarization of human microglia inhibited a store-operated pathway for entry of Ca2+. We have used Fura-2 spectrofluorometry to investigate the effects on store-operated Ca2+ influx induced by replacement of NaCl with Na-gluconate in extracellular solutions. Three separate procedures were used to activate store-operated channels. Platelet activating factor (PAF) was used to generate a sustained influx of Ca2+ in standard physiological saline solution (PSS). The magnitude of this response was depressed by 70% after replacement of PSS with low Cl- PSS. A second procedure used ATP, initially applied in Ca2+-free PSS solution to deplete intracellular stores. The subsequent perfusion of PSS solution containing Ca2+ resulted in a large and sustained entry of Ca2+, which was inhibited by 75% with low Cl- PSS. The SERCA inhibitor cyclopiazonic acid (CPA) was used to directly deplete stores in zero-Ca2+ PSS. Following the introduction of PSS containing Ca2+, a maintained stores-operated influx of Ca2+ was evident which was inhibited by 77% in the presence of the low Cl- PSS. Ca2+ influx was linearly reduced with cell depolarization in elevated K+ (7.5 to 35 mM) suggesting that changes in external Cl- were manifest as altered electrical driving force for Ca2+ entry. However, 50 mM external KCl effectively eliminated divalent entry which may indicate inactivation of this pathway with high magnitudes of depolarization. Patch clamp studies showed low Cl-PSS to cause depolarizing shifts in both holding currents and reversal potentials of currents activated with voltage ramps. The results demonstrate that Cl- channels play an important role in regulating store-operated entry of Ca2+ in human microglia.

Authors+Show Affiliations

Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. Mclarnon@interchange.ubc.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11032781

Citation

McLarnon, J G., et al. "Anion Channels Modulate Store-operated Calcium Influx in Human Microglia." Cell Calcium, vol. 28, no. 4, 2000, pp. 261-8.
McLarnon JG, Helm J, Goghari V, et al. Anion channels modulate store-operated calcium influx in human microglia. Cell Calcium. 2000;28(4):261-8.
McLarnon, J. G., Helm, J., Goghari, V., Franciosi, S., Choi, H. B., Nagai, A., & Kim, S. U. (2000). Anion channels modulate store-operated calcium influx in human microglia. Cell Calcium, 28(4), 261-8.
McLarnon JG, et al. Anion Channels Modulate Store-operated Calcium Influx in Human Microglia. Cell Calcium. 2000;28(4):261-8. PubMed PMID: 11032781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anion channels modulate store-operated calcium influx in human microglia. AU - McLarnon,J G, AU - Helm,J, AU - Goghari,V, AU - Franciosi,S, AU - Choi,H B, AU - Nagai,A, AU - Kim,S U, PY - 2000/10/18/pubmed PY - 2001/3/3/medline PY - 2000/10/18/entrez SP - 261 EP - 8 JF - Cell calcium JO - Cell Calcium VL - 28 IS - 4 N2 - Recent work from this laboratory has demonstrated that purinergic-mediated depolarization of human microglia inhibited a store-operated pathway for entry of Ca2+. We have used Fura-2 spectrofluorometry to investigate the effects on store-operated Ca2+ influx induced by replacement of NaCl with Na-gluconate in extracellular solutions. Three separate procedures were used to activate store-operated channels. Platelet activating factor (PAF) was used to generate a sustained influx of Ca2+ in standard physiological saline solution (PSS). The magnitude of this response was depressed by 70% after replacement of PSS with low Cl- PSS. A second procedure used ATP, initially applied in Ca2+-free PSS solution to deplete intracellular stores. The subsequent perfusion of PSS solution containing Ca2+ resulted in a large and sustained entry of Ca2+, which was inhibited by 75% with low Cl- PSS. The SERCA inhibitor cyclopiazonic acid (CPA) was used to directly deplete stores in zero-Ca2+ PSS. Following the introduction of PSS containing Ca2+, a maintained stores-operated influx of Ca2+ was evident which was inhibited by 77% in the presence of the low Cl- PSS. Ca2+ influx was linearly reduced with cell depolarization in elevated K+ (7.5 to 35 mM) suggesting that changes in external Cl- were manifest as altered electrical driving force for Ca2+ entry. However, 50 mM external KCl effectively eliminated divalent entry which may indicate inactivation of this pathway with high magnitudes of depolarization. Patch clamp studies showed low Cl-PSS to cause depolarizing shifts in both holding currents and reversal potentials of currents activated with voltage ramps. The results demonstrate that Cl- channels play an important role in regulating store-operated entry of Ca2+ in human microglia. SN - 0143-4160 UR - https://www.unboundmedicine.com/medline/citation/11032781/Anion_channels_modulate_store_operated_calcium_influx_in_human_microglia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4160(00)90150-7 DB - PRIME DP - Unbound Medicine ER -