Celecoxib and ion channels: A story of unexpected discoveries

Celecoxib (Celebrex), a highly popular selective inhibitor of cyclooxygenase-2, can modulate ion channels and alter functioning of neurons and myocytes at clinically relevant concentrations independently of cyclooxygenase inhibition. In experimental systems varying from Drosophila to primary mammalian and human cell lines, celecoxib inhibits many voltage-activated Na⁺, Ca²⁺, and K⁺ channels, including Na_V1.5, L- and T-type Ca²⁺ channels, K_V1.5, K_V2.1, K _V4.3, K_V7.1, K_V11.1 (hERG), while stimulating other K⁺ channels-K_V7.2-5 and, possibly, K_V11.1 (hERG) channels under certain conditions. In this review, we summarize the information currently available on the effects of celecoxib on ion channels, examine mechanistic aspects of drug action and the concomitant changes at the cellular and organ levels, and discuss these findings in the therapeutic context.