Authors: Alagu Thiruvengadam.
Lithium is an effective mood stabilizer in 70-80 percent of bipolar disorder patients. It has been observed that the membrane potential is hyperpolarized in bipolar patients and lithium treatment depolarizes it. Hokin and his colleagues found that the lithium increases accumulation of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) in brain cortex slices in species ranging from mouse to monkey. DAG and IP3 activate the DAG signaling pathway depolarizing the membrane potential. The DAG signaling pathway regulates the calcium activated potassium (CAK) channels. The CAK channels in turn control the membrane potentials and excitabilities of neurons. The clinical observations that the membrane potential is hyperpolarized (lower) in bipolar disorder patients and lithium depolarizes (increases) are explained using the action of DAG signaling pathway. Lithium increases the concentration of DAG thereby increasing the activity of DAG signaling pathway which controls the potassium flow through the CAK channel. If this result is established through further independent corroboration it would greatly enhance our understanding of the mechanisms of bipolar disorder. Knowledge of this signaling pathway elucidates how lithium treats bipolar disorder.
Additionally, the mechanism of induced switching associated with certain antidepressants given to patients who are bipolar can also be explained by this pathway. Further analysis of this pathway would lead to the discovery of new drugs for this disease.