Effects of celecoxib on ionic currents and spontaneous firing in rat retinal neurons

Accumulating evidence suggests that the side effects of celecoxib, widely used to treat muscle and joint pain, may be mediated in part through cyclooxygenase-2 (COX-2) independent mechanisms, such as inhibition of ion channels. In this study we report effects of celecoxib on ionic currents and neuronal activity in isolated rat retinal neurons. We found that celecoxib suppressed voltage-gated potassium currents in retinal bipolar cells with an effective concentration to inhibit 50% of function (EC(50)) of 5.5 microM. In retinal amacrine and ganglion cells, celecoxib inhibited voltage-dependent sodium channels with an EC(50) of 5.2 microM, and voltage-dependent transient and sustained potassium currents with EC(50)s of 16.3 and 9.1 microM, respectively. Notably, the rate of spontaneous spike activity was dramatically suppressed in ganglion and amacrine cells with an EC(50) of 0.76 microM. All actions of celecoxib on ionic currents and action potentials occurred from the extracellular side and were completely reversible. These findings indicate that inhibition of ion channels by celecoxib in the CNS may affect neuronal function at clinically relevant concentrations.