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Abstract #6866 Published in IGR 4-1
Flufenamic acid enhances current through maxi-K channels in the trabecular meshwork of the eye
Stumpff F; Boxberger M; Thieme H; Strauss O; Wiederholt MCurrent Eye Research 2001; 22: 427-437
PURPOSE: Flufenamic acid relaxes the trabecular meshwork, a smooth muscle-like tissue involved in the regulation of ocular outflow in the eye. In this study, the authors attempted to determine whether ionic channels are involved in this response. METHODS: Cultured human (HTM) and bovine (BTM) trabecular meshwork cells were investigated using the patch-clamp technique. RESULTS: In the trabecular meshwork, flufenamic acid (10-5 M) reversibly stimulated the outward current to 406 ± 71% of the initial outward current level in BTM (n = 10) and 294 ± 75% of the initial current level in HTM (n = 12) in all cells investigated; no significant differences were seen. The response was dosage-dependent. Replacement of potassium in all solutions eliminated the response to flufenamic acid (n = 4, BTM). Blocking KATP channels with glibenclamide (10-5 M, n = 6) and small-conductance calcium-activated potassium channels with apamin (10-6 M, n = 5) had no effect. No direct effect on calcium channels could be detected either. Blockage of the large-conductance calcium-activated potassium channel (maxi-K) by iberiotoxin (10-7 M) suppressed 87 ± 9% (n = 6; HTM) and 91 ± 10% (n = 6; BTM) of the response. Depleting the cells of calcium did not significantly alter the response to flufenamic acid. CONCLUSIONS: Flufenamic acid stimulates maxi-K channels in both human and bovine trabecular meshwork. 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.
Dr. F. Stumpff, Institut fur Klinische Physiologie, Univ.klinikum Benjamin Franklin, Freie Universitat Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. stumpff@zedat.fu-berlin.de
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)