A1 Refereed original research article in a scientific journal
Ca2+-dependent potentiation of muscarinic receptor-mediated Ca2+ elevation
Authors: Akerman KEO, Shariatmadari R, Krjukova J, Larsson KP, Courtney MJ, Kukkonen JP
Publisher: CHURCHILL LIVINGSTONE
Publication year: 2004
Journal: Cell Calcium
Journal name in source: CELL CALCIUM
Journal acronym: CELL CALCIUM
Volume: 36
Issue: 5
First page : 397
Last page: 408
Number of pages: 12
ISSN: 0143-4160
DOI: https://doi.org/10.1016/j.ceca.2004.03.003
Abstract
Muscarinic receptor-mediated increases in Ca2+ in SH-SY5Y neuroblastoma cells consist of an initial fast and transient phase followed by a sustained phase. Activation of voltage-gated Ca2+ channels prior to muscarinic stimulation resulted in a several-fold potentiation of the fast phase. Unlike the muscarinic response under control conditions, this potentiated elevation of intracellular Ca2+ was to a large extent dependent on extracellular Ca2+. In potentiated cells, muscarinic stimulation also activated a rapid Mn2+ entry. By using known organic and inorganic blockers of cation channels, this influx pathway was easily separated from the known Ca2+ influx pathways, the store-operated pathway and the voltage-gated Ca2+ channels. In addition to the Ca2+ influx, both IP3 production and Ca2+ release were also enhanced during the potentiated response. The results suggest that a small increase in intracellular Ca2+ amplifies the muscarinic Ca2+ response at several stages, most notably by unravelling an apparently novel receptor-activated influx pathway. (C) 2004 Elsevier Ltd. All rights reserved.
Muscarinic receptor-mediated increases in Ca2+ in SH-SY5Y neuroblastoma cells consist of an initial fast and transient phase followed by a sustained phase. Activation of voltage-gated Ca2+ channels prior to muscarinic stimulation resulted in a several-fold potentiation of the fast phase. Unlike the muscarinic response under control conditions, this potentiated elevation of intracellular Ca2+ was to a large extent dependent on extracellular Ca2+. In potentiated cells, muscarinic stimulation also activated a rapid Mn2+ entry. By using known organic and inorganic blockers of cation channels, this influx pathway was easily separated from the known Ca2+ influx pathways, the store-operated pathway and the voltage-gated Ca2+ channels. In addition to the Ca2+ influx, both IP3 production and Ca2+ release were also enhanced during the potentiated response. The results suggest that a small increase in intracellular Ca2+ amplifies the muscarinic Ca2+ response at several stages, most notably by unravelling an apparently novel receptor-activated influx pathway. (C) 2004 Elsevier Ltd. All rights reserved.
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