Ottolia M, Toro L
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Biophys J. 1994 Dec;67(6):2272-9. doi: 10.1016/S0006-3495(94)80712-X.
Large conductance calcium-activated K+ (KCa) channels are rapidly activated by niflumic acid dose-dependently and reversibly. External niflumic acid was about 5 times more potent than internal niflumic acid, and its action was characterized by an increase in the channel affinity for [Ca2+], a parallel left shift of the voltage-activation curve, and a decrease of the channel long-closed states. Niflumic acid applied from the external side did not interfere with channel block by charybdotoxin, suggesting that its site of action is not at or near the charybdotoxin receptor. Accordingly, partial tetraethylammonium blockade did not interfere with channel activation by niflumic acid. Flufenamic acid and mefenamic acid also stimulated KCa channel activity and, as niflumic acid, they were more potent from the external than from the internal side. Fenamates applied from the external side displayed the following potency sequence: flufenamic acid approximately niflumic acid >> mefenamic acid. These results indicate that KCa channels possess at least one fenamatereceptor whose occupancy leads to channel opening.
大电导钙激活钾（KCa）通道可被氟尼辛剂量依赖性且可逆地快速激活。细胞外氟尼辛的作用效力约为细胞内氟尼辛的5倍，其作用表现为通道对[Ca2+]的亲和力增加、电压激活曲线平行左移以及通道长关闭状态减少。从细胞外侧施加氟尼辛并不干扰蝎毒素对通道的阻断作用，这表明其作用位点不在蝎毒素受体处或其附近。因此，部分四乙铵阻断并不干扰氟尼辛对通道的激活。氟芬那酸和甲芬那酸也能刺激KCa通道活性，并且与氟尼辛一样，它们从细胞外侧施加时比从细胞内侧施加时效力更强。从细胞外侧施加的芬那酸盐呈现出以下效力顺序：氟芬那酸≈氟尼辛>>甲芬那酸。这些结果表明，KCa通道至少拥有一个芬那酸受体，占据该受体可导致通道开放。
