Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bipolar Disorder* / drug therapy
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Bipolar Disorder* / metabolism
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Bipolar Disorder* / physiopathology
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Calcium / metabolism*
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Calcium Channels / genetics
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Calcium Channels / metabolism*
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Calcium Signaling / physiology*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Electrophysiology
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Humans
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In Vitro Techniques
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Inositol 1,4,5-Trisphosphate Receptors
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Lithium* / metabolism
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Lithium* / therapeutic use
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Mice
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Neuronal Calcium-Sensor Proteins
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Neurons / cytology
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Neurons / metabolism
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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PC12 Cells
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Rats
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Ryanodine Receptor Calcium Release Channel / metabolism
Substances
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Calcium Channels
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Calcium-Binding Proteins
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ITPR1 protein, human
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Inositol 1,4,5-Trisphosphate Receptors
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Neuronal Calcium-Sensor Proteins
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Neuropeptides
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Receptors, Cytoplasmic and Nuclear
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Ryanodine Receptor Calcium Release Channel
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frequenin calcium sensor proteins
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Lithium
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Calcium