uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Ca2+-Dependent Potentiation of Muscarinic Receptor-Mediated Ca2+ Elevation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Show others and affiliations
2004 (English)In: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 36, no 5, 397-408 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
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
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91903DOI: 10.1016/j.ceca.2004.03.003PubMedID: 15451623OAI: oai:DiVA.org:uu-91903DiVA: diva2:164780
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2013-07-10Bibliographically approved
In thesis
1. Investigation on Pre- and Postsynaptic Ca2+ Signaling in Neuronal Model Systems
Open this publication in new window or tab >>Investigation on Pre- and Postsynaptic Ca2+ Signaling in Neuronal Model Systems
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Communication between neuronal and non-neuronal is called volume transmission when the released neurotransmitter (NT) acts via diffusion and affects several target cells. Both the neurosecretory and postsynaptic cell responses are linked to [Ca2+]i elevations.

In the present thesis the role of pre-and postsynaptic Ca2+ elevations has been investigated in the reconstituted "synapse" model comprised of NGF-differentiated PC12 and HEL cells as well as in SH-SY5Y neuroblastoma cells. In PC12 cells, both 70mM K+ and nicotine triggered NT release, which could be detected as a secondary [Ca2+]i increase in surrounding HEL cells. Both secretagogues shared the same voltage-dependent Ca2+ influx pathway as judged from the pharmacological profile blockers of voltage-gated Ca2+ channels. The coupling of electrical responses to the activation of Ca2+ signaling via muscarinic receptors in SH-SY5Y cells was also studied. These data revealed that depolarization caused a considerable potentiation of the muscarinic Ca2+ response. The potentiated Ca2+ increase was mainly dependent on the enhanced Ca2+ influx and to a lesser extent on [Ca2+]i release from intracellular stores. A phospholipase C (PLC) activator, m-3M3FBS was used to further study the role of G-protein coupled receptor (GPCR)-coupled Ca2+ signaling. However, it was found that m-3M3FBS instead triggered [Ca2+]i elevations independently of PLC activation.

In conclusion, the results indicate that the magnitude of NT release from PC12 cells is sufficient to cause a robust activation of neighboring target cells. Postsynaptic muscarinic signaling is amplified due to integration of electrical excitation and GPCR signaling. The PLC activator, m-3M3FBS is not suitable for studies of PLC-mediated signals in intact cells.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 52 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1361
Keyword
Physiology, calcium, neurotransmitter release, nicotine, depolarization, G-protein coupled receptor, muscarinic, phospholipase C, m-3M3FBS, Fysiologi
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-4300 (URN)91-554-5993-5 (ISBN)
Public defence
2004-06-05, Room B21, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-05-12 Created: 2004-05-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Physiology
In the same journal
Cell Calcium
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 494 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf