Flufenamic acid enhances current through maxi-K channels in the trabecularmeshwork of the eye

Purpose. Flufenamic acid relaxes trabecular meshwork, a smooth muscle-like tissue involved in the regulation of ocular outflow in the eye. In this stu dy, we attempted to determine if ionic channels are involved in this respon se. Methods. Cultured human (HTM) and bovine (BTM) trabecular meshwork cells we re investigated using the patch-clamp technique. Results. In trabecular meshwork, flufenamic acid (10(-5)M) reversibly stimu lated outward current to 406 +/- 71% of initial outward current level in BT M (n = 10) and 294 +/- 75% of initial current level in HTM (n = 12) in all cells investigated; no significant differences emerged. The response was do sage-dependent. Replacement of potassium in all solutions eliminated the re sponse to flufenamic acid (n = 4, BTM). Blocking K-ATP channels with gliben clamide (10 (5) M, n = 6) and small-conductance calcium-activated potassium channels with apamin (10(-6) M, n = 5) had no effect. A direct effect on c alcium channels could also not be detected. Blockage of the large-conductan ce calcium-activated potassium channel (maxi-K) by iberiotoxin (10(-7) M) s uppressed 87 +/- 9% (n = 6; HTM) and 91 +/- 10% (n = 6; BTM) of the respons e. Depleting the cells of calcium did not significantly alter the response to flufenamic acid. Conclusions. Flufenamic acid stimulates maxi-K channels in trabecular meshw ork of both human and bovine origin. This should lead to hyperpolarization, closure of L-type channels and lowered cytosolic calcium levels, possibly explaining the relaxation observed in response to this substance.