Abstract
Celecoxib, a selective inhibitor of cyclooxygenase-2, can directly modulate many voltage-activated potassium, sodium and calcium channels and alter functioning of excitable cells. The inhibitory and facilitating effects of celecoxib on ion channels occur at low micromolar concentrations, bordering on therapeutic concentrations achievable in the clinical setting. The experiments described here were performed with the goals (1) to increase the range of ion channels tested, and (2) to examine possible differences in celecoxib's effects on channels from different species. The channels examined in this study using patch-clamp and intracellular recording methods were human KV1.3 channels expressed in CHO cells, L-type Ca(2+) channels (LTCC) from guinea pig cardiomyocytes, and LTCCs from Drosophila larval body-wall muscles. Celecoxib inhibited KV1.3 currents with IC50 of 5.0 μM at the end of 200 ms pulses to +20 mV. Celecoxib inhibited peak currents through guinea pig and Drosophila LTCCs with IC50s of 10.6 and 76.0 μM, respectively. As blockade of KV1.3 channels is associated with suppression of inflammatory immune reactions, the finding that celecoxib can inhibit these channels raises a question of possible contribution of KV1.3 inhibition to the anti-inflammatory effects of celecoxib. On the other hand, the Ca(2+) channel results are consistent with previous observations indicating that, in contrast to K(+) channels, strength of celecoxib effects on LTCCs strongly varies from species to species.
