Chronic oxidative stress modulates TRPC3 and TRPM2 channel expression and function in rat primary cortical neurons: Relevance to the pathophysiology of bipolar disorder

Abstract Recent findings implicate the calcium-permeable transient receptor potential (TRP) melastatin subtype 2 (TRPM2) and canonical subtype 3 (TRPC3) channels in the pathogenesis of bipolar disorder (BD). As both channels are involved in calcium and oxidative stress signaling, thought to be disrupted in BD, we sought to determine the effects of elevated oxidative stress on their expression and function. Primary rat cortical neurons and astrocytes were treated with oxidative stressors for 1 (acute) and 4 days (chronic). Expression of TRPC3 and TRPM2 were determined by immunoblotting and real-time PCR. Channel functionality was assessed using a TRPC3 activator, 1-oleoyl-2-acetyl-sn-glycerol (OAG), and live cell, ratiometric fluorometry with the calcium sensitive dye, Fura-2. Neurons treated with rotenone (15–30 nM) for 4 days but not 24 h showed significant dose-dependent decreases in TRPC3 mRNA (31%, p