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Beta-amyloid enhances intracellular calcium rises mediated by repeated activation of intracellular calcium stores and nicotinic receptors in acutely dissociated rat basal forebrain neurons.
Brain Cell Biol. 2006 Jun; 35(2-3):173-86.BC

Abstract

Beta-amyloid, a 39-43 amino acid peptide, may exert its biological effects via neuronal nicotinic acetylcholine receptors. Using the ratiometric dye, fura-2, we examined the effect of soluble beta-amyloid(1-42) on the concentration of intracellular Ca(2+) ([Ca(2+)](i)) in acutely dissociated rat basal forebrain neurons. Focal applications of nicotine (0.5-20 mM), evoked dose-dependent increases in intracellular [Ca(2+)](i) that were mediated by the entry of extracellular Ca(2+) via nicotinic acetylcholine receptors, and the release of intracellular Ca(2+) from stores. With repeated nicotine challenges, the nicotinic responses were potentiated by 98 +/- 12% (P < 0.05) while beta-amyloid(1-42)(100 nM) was present for approximately 5 min. This potentiation became larger during the subsequent washout of beta-amyloid(1-42), which was associated with a gradual rise in baseline [Ca(2+)](i). Application of beta-amyloid(1-42)by itself did not alter [Ca(2+)](i), and beta-amyloid(1-42)also had no significant effect on the response to repeated KCl challenges. Therefore, beta-amyloid(1-42) caused neither gross disturbance of cellular Ca(2+) homeostasis nor enhancement of voltage-gated Ca(2+) channels. Interestingly, beta-amyloid(1-42) transiently potentiated the response to repeated caffeine challenges, which was also associated with a transient rise in baseline [Ca(2+)](i). beta-amyloid(1-42) potentiation of nicotine-evoked rises in [Ca(2+)](i) was reversed by the SERCA pump inhibitor, thapsigargin, and the mitochondrial Na(+)/Ca(2+) exchanger inhibitor, CGP-37157. These results suggest that the dysregulation of [Ca(2+)](i) by beta-amyloid(1-42) during multiple challenges with nicotine or caffeine involved the sensitization or overfilling of intracellular stores that are maintained by SERCA pump and Ca(2+) efflux from the mitochondria.

Authors+Show Affiliations

Department of Medicine, Division of Neurology, University of Alberta, 530 Heritage Medical Research Centre, Edmonton, AB, Canada T6G 2S2.No 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

17957482

Citation

Chin, James H., et al. "Beta-amyloid Enhances Intracellular Calcium Rises Mediated By Repeated Activation of Intracellular Calcium Stores and Nicotinic Receptors in Acutely Dissociated Rat Basal Forebrain Neurons." Brain Cell Biology, vol. 35, no. 2-3, 2006, pp. 173-86.
Chin JH, Tse FW, Harris K, et al. Beta-amyloid enhances intracellular calcium rises mediated by repeated activation of intracellular calcium stores and nicotinic receptors in acutely dissociated rat basal forebrain neurons. Brain Cell Biol. 2006;35(2-3):173-86.
Chin, J. H., Tse, F. W., Harris, K., & Jhamandas, J. H. (2006). Beta-amyloid enhances intracellular calcium rises mediated by repeated activation of intracellular calcium stores and nicotinic receptors in acutely dissociated rat basal forebrain neurons. Brain Cell Biology, 35(2-3), 173-86.
Chin JH, et al. Beta-amyloid Enhances Intracellular Calcium Rises Mediated By Repeated Activation of Intracellular Calcium Stores and Nicotinic Receptors in Acutely Dissociated Rat Basal Forebrain Neurons. Brain Cell Biol. 2006;35(2-3):173-86. PubMed PMID: 17957482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Beta-amyloid enhances intracellular calcium rises mediated by repeated activation of intracellular calcium stores and nicotinic receptors in acutely dissociated rat basal forebrain neurons. AU - Chin,James H, AU - Tse,Frederick W, AU - Harris,Kim, AU - Jhamandas,Jack H, Y1 - 2007/10/04/ PY - 2006/12/08/received PY - 2007/03/14/accepted PY - 2007/03/07/revised PY - 2007/10/25/pubmed PY - 2008/1/12/medline PY - 2007/10/25/entrez SP - 173 EP - 86 JF - Brain cell biology JO - Brain Cell Biol VL - 35 IS - 2-3 N2 - Beta-amyloid, a 39-43 amino acid peptide, may exert its biological effects via neuronal nicotinic acetylcholine receptors. Using the ratiometric dye, fura-2, we examined the effect of soluble beta-amyloid(1-42) on the concentration of intracellular Ca(2+) ([Ca(2+)](i)) in acutely dissociated rat basal forebrain neurons. Focal applications of nicotine (0.5-20 mM), evoked dose-dependent increases in intracellular [Ca(2+)](i) that were mediated by the entry of extracellular Ca(2+) via nicotinic acetylcholine receptors, and the release of intracellular Ca(2+) from stores. With repeated nicotine challenges, the nicotinic responses were potentiated by 98 +/- 12% (P < 0.05) while beta-amyloid(1-42)(100 nM) was present for approximately 5 min. This potentiation became larger during the subsequent washout of beta-amyloid(1-42), which was associated with a gradual rise in baseline [Ca(2+)](i). Application of beta-amyloid(1-42)by itself did not alter [Ca(2+)](i), and beta-amyloid(1-42)also had no significant effect on the response to repeated KCl challenges. Therefore, beta-amyloid(1-42) caused neither gross disturbance of cellular Ca(2+) homeostasis nor enhancement of voltage-gated Ca(2+) channels. Interestingly, beta-amyloid(1-42) transiently potentiated the response to repeated caffeine challenges, which was also associated with a transient rise in baseline [Ca(2+)](i). beta-amyloid(1-42) potentiation of nicotine-evoked rises in [Ca(2+)](i) was reversed by the SERCA pump inhibitor, thapsigargin, and the mitochondrial Na(+)/Ca(2+) exchanger inhibitor, CGP-37157. These results suggest that the dysregulation of [Ca(2+)](i) by beta-amyloid(1-42) during multiple challenges with nicotine or caffeine involved the sensitization or overfilling of intracellular stores that are maintained by SERCA pump and Ca(2+) efflux from the mitochondria. SN - 1559-7105 UR - https://www.unboundmedicine.com/medline/citation/17957482/Beta_amyloid_enhances_intracellular_calcium_rises_mediated_by_repeated_activation_of_intracellular_calcium_stores_and_nicotinic_receptors_in_acutely_dissociated_rat_basal_forebrain_neurons_ L2 - https://dx.doi.org/10.1007/s11068-007-9010-7 DB - PRIME DP - Unbound Medicine ER -