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

• Published in: Neuroscience Vol. 154; no. 4; pp. 1525 - 1532
• Main Authors: Frolov, R.V, Slaughter, M.M, Singh, S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 17.07.2008; Elsevier
• Subjects: Action Potentials - drug effects; Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Biological and medical sciences; Celecoxib; coxibs; electrophysiology; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Neurology; Patch-Clamp Techniques; pharmacology; potassium channels; Potassium Channels, Voltage-Gated - drug effects; Pyrazoles - toxicity; Rats; Retinal Neurons - drug effects; sodium channels; Sodium Channels - drug effects; Sulfonamides - toxicity; Vertebrates: nervous system and sense organs; voltage-gated channels; fast transient current; half-activation potential; voltage-gated channels; sustained current; effective concentration to inhibit 50% of function; V a 1/2; 4-aminopyridine; sodium channels; potassium channels; pharmacology; ethylenediaminetetraacetic acid; TTX; liquid chromatography; coxibs; EDTA; nuclear magnetic resonance; 4-AP; TEA; NMR; electrophysiology; EC 50; tetraethylammonium; LC; tetrodotoxin; I T; I S; Va1/2; IS; IT; EC50; voltage- gated channels; Rat; Rodentia; Electrophysiology; Retina; Ionic channel; Ionic current; Celecoxib; Eye; Visual system; Vertebrata; Mammalia; Neuron; Sodium; Animal; Potassium
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.05.004

Abstract 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 (EC50 ) of 5.5 μM. In retinal amacrine and ganglion cells, celecoxib inhibited voltage-dependent sodium channels with an EC50 of 5.2 μM, and voltage-dependent transient and sustained potassium currents with EC50 s of 16.3 and 9.1 μM, respectively. Notably, the rate of spontaneous spike activity was dramatically suppressed in ganglion and amacrine cells with an EC50 of 0.76 μM. 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.