Bipolar Research Today is a free monthly online journal that collates and summarizes the latest research about Bipolar, including details on bipolar disorder, symptoms, treatment, depression, medication.

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

Schlecker C, Boehmerle W, Jeromin A, DeGray B, Varshney A, Sharma Y, Szigeti-Buck K, Ehrlich BE

Department of Pharmacology, Yale University, New Haven, Connecticut 06520-8066, USA.

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.

Published 2 June 2006 in J Clin Invest, 116(6): 1668-74.
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