TY - JOUR
T1 - Muscarinic receptor activation determines the effects of store-operated Ca2+-entry on excitability and energy metabolism in pyramidal neurons
AU - Kann, Oliver
AU - Taubenberger, Nando
AU - Huchzermeyer, Christine
AU - Papageorgiou, Ismini E.
AU - Benninger, Felix
AU - Heinemann, Uwe
AU - Kovács, Richard
N1 - Funding Information:
The authors thank Kristin Lehmann for excellent technical support and Andrea Lewen for text editing assistance. This work was supported by Deutsche Forschungsgemeinschaft in SFB 618 and SFB TR-3, Hertie-Stiftung and Exzellenzcluster NeuroCure .
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - Acetylcholine
KW - Capacitative calcium entry
KW - Hippocampus
KW - Mitochondria
KW - NADH
KW - Oxidative metabolism
KW - Potassium concentration [K]
KW - Store-operated calcium entry
UR - http://www.scopus.com/inward/record.url?scp=84856078073&partnerID=8YFLogxK
U2 - 10.1016/j.ceca.2011.10.004
DO - 10.1016/j.ceca.2011.10.004
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C2 - 22088219
AN - SCOPUS:84856078073
SN - 0143-4160
VL - 51
SP - 40
EP - 50
JO - Cell Calcium
JF - Cell Calcium
IS - 1
ER -