Decreased levels of canonical transient receptor potential channel 3 protein in the rat cerebral cortex after chronic treatment with lithium or valproate

Abstract

Lithium and valproate modulate disturbances in intracellular calcium homeostasis implicated in the pathophysiology of bipolar disorder, but the molecular mechanisms are not fully understood. Two subtypes of transient receptor potential (TRP) channel family, i.e. TRPC3 and TRPM2, are potential candidates involved in calcium signaling and implicated in the pathophysiology of bipolar disorder. This study was designed to investigate whether mood stabilizers such as lithium and valproate affect the expression of TRPC3 and TRPM2. Rats were treated with intraperitoneal injections of lithium (2 mEq/kg b.i.d.) or valproate (300 mg/kg b.i.d.) acutely (for 24 h) or chronically (for 4 weeks). The changes in mRNA and protein levels of TRPC3 and TRPM2 were measured with real-time polymerase chain reaction and western blotting. The chronic administration of lithium and valproate significantly reduced levels of TRPC3 by 19.7% and 19.3%, respectively. No change was detected in the mRNA level of this channel. Neither acute nor chronic treatment with lithium or valproate had any effect on TRPM2 levels. The results suggest that downregulation of the TRPC3 channel is an important shared mechanism by which lithium and valproate can modulate calcium disturbances, whereas the TRPM2 channel does not appear to be affected by mood stabilizers, at least under non stressed conditions.