Ca2+-Dependent Potentiation of Muscarinic Receptor-Mediated Ca2+ Elevation
2004 (English)In: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 36, no 5, 397-408 p.Article in journal (Refereed) Published
Muscarinic receptor-mediated increases in Ca(2+) in SH-SY5Y neuroblastoma cells consist of an initial fast and transient phase followed by a sustained phase. Activation of voltage-gated Ca(2+) 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 Ca(2+) was to a large extent dependent on extracellular Ca(2+). In potentiated cells, muscarinic stimulation also activated a rapid Mn(2+) entry. By using known organic and inorganic blockers of cation channels, this influx pathway was easily separated from the known Ca(2+) influx pathways, the store-operated pathway and the voltage-gated Ca(2+) channels. In addition to the Ca(2+) influx, both IP(3) production and Ca(2+) release were also enhanced during the potentiated response. The results suggest that a small increase in intracellular Ca(2+) amplifies the muscarinic Ca(2+) response at several stages, most notably by unravelling an apparently novel receptor-activated influx pathway.
Place, publisher, year, edition, pages
2004. Vol. 36, no 5, 397-408 p.
Calcium/*metabolism/physiology, Calcium Channels/physiology, Calcium Signaling/drug effects/*physiology, Carbachol/pharmacology, Cell Line; Tumor, Comparative Study, Dose-Response Relationship; Drug, Humans, Receptors; Muscarinic/*physiology, Research Support; Non-U.S. Gov't
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-91903DOI: 10.1016/j.ceca.2004.03.003PubMedID: 15451623OAI: oai:DiVA.org:uu-91903DiVA: diva2:164780