Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, ca...

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Bibliographic Details
Published in:The Journal of clinical investigation 2006-06, Vol.116 (6), p.1668-1674
Main Authors: Schlecker, Christina, Boehmerle, Wolfgang, Jeromin, Andreas, DeGray, Brenda, Varshney, Anurag, Sharma, Yogendra, Szigeti-Buck, Klara, Ehrlich, Barbara E
Format: Article
Language:English
Subjects:
Animals
Bipolar Disorder - drug therapy
Bipolar Disorder - metabolism
Bipolar Disorder - physiopathology
Calcium - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Calcium Signaling - physiology
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
Electrophysiology
Humans
In Vitro Techniques
Inositol 1,4,5-Trisphosphate Receptors
Lithium - metabolism
Lithium - therapeutic use
Mice
Neuronal Calcium-Sensor Proteins
Neurons - cytology
Neurons - metabolism
Neuropeptides - genetics
Neuropeptides - metabolism
PC12 Cells
Rats
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Ryanodine Receptor Calcium Release Channel - metabolism
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Summary:Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding protein, to purified InsP3R type 1 (InsP3R1) increased the channel activity in both a calcium-dependent and -independent manner. In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway. To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders. Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI22466