Muscarinic receptor activation determines the effects of store-operated Ca2+-entry on excitability and energy metabolism in pyramidal neurons

In various cell types, depletion of intracellular Ca2+-stores results in store-operated Ca2+-entry (SOCE) across the cellular membrane. However, the effects of SOCE on neuronal membrane excitability and mitochondrial functions in central neurons are not well defined. We investigated such cellular do...

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Bibliographic Details
Main Authors: Kann, Oliver (Author) , Papageorgiou, Ismini E. (Author)
Format: Article (Journal)
Language:English
Published: 2012
In: Cell calcium
Year: 2011, Volume: 51, Issue: 1, Pages: 40-50
ISSN:1532-1991
DOI:10.1016/j.ceca.2011.10.004
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.ceca.2011.10.004
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0143416011002016
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Author Notes:Oliver Kann, Nando Taubenberger, Christine Huchzermeyer, Ismini E. Papageorgiou, Felix Benninger, Uwe Heinemann, Richard Kovács
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Summary:In various cell types, depletion of intracellular Ca2+-stores results in store-operated Ca2+-entry (SOCE) across the cellular membrane. However, the effects of SOCE on neuronal membrane excitability and mitochondrial functions in central neurons are not well defined. We investigated such cellular downstream effects in pyramidal neurons of rat organotypic hippocampal slice cultures by applying electrophysiological and fluorescence imaging techniques. We report that SOCE is associated with (i) elevations of Ca2+-concentration in individual neuronal mitochondria ([Ca2+]m). In addition, SOCE can result in (ii) hyperpolarizing neuronal membrane currents, (iii) increase in extracellular K+-concentration ([K+]o), (iv) mitochondrial membrane depolarization, and (v) changes in intracellular redox state (NAD(P)H and FAD fluorescence), the latter reflecting responses of energy metabolism. These additional downstream effects of SOCE required concomitant muscarinic receptor activation by carbachol or acetylcholine, and were suppressed by agonist washout or application of antagonist, atropine. We conclude that muscarinic receptor activation determines the downstream effects of SOCE on neuronal membrane excitability and energy metabolism. This mechanism might have significant impact on information processing and neurometabolic coupling in central neurons.
Item Description:Available online 14 November 2011
Available online 14 November 2011
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Im Titel ist 2+ hochgestellt
Physical Description:Online Resource
ISSN:1532-1991
DOI:10.1016/j.ceca.2011.10.004