POTENTIATION OF LARGE-CONDUCTANCE K-CA CHANNELS BY NIFLUMIC, FLUFENAMIC, AND MEFENAMIC ACIDS
POTENTIATION OF LARGE-CONDUCTANCE K-CA CHANNELS BY NIFLUMIC, FLUFENAMIC, AND MEFENAMIC ACIDS
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DOI：
10.1016/s0006-3495(94)80712-x
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发表时间：
1994-12-01
影响因子：
3.4
通讯作者：
TORO, L
中科院分区：
文献类型：
--
作者：
OTTOLIA, M;TORO, L
大电导钙激活 K+ (K-Ca) 通道可被尼氟酸快速激活，且呈剂量依赖性且可逆。外部尼氟酸的效力比内部尼氟酸强约5倍，其作用特征是通道对[Ca2+]亲和力的增加、电压激活曲线的平行左移以及通道长关闭状态的减少。从外侧施加的尼氟酸不会干扰卡雷布毒素的通道阻断，表明其作用位点不在卡雷布毒素受体处或附近。因此，部分四乙铵阻断不会干扰尼氟酸的通道激活。氟芬那酸和甲芬那酸也刺激 K-Ca 通道活性，并且与尼氟酸一样，它们从外部比从内部更有效。从外侧施用芬那酯显示出以下效力顺序：氟芬那酸近似于尼氟酸>>甲芬那酸。这些结果表明 K-Ca 通道具有至少一种 fenamate 受体，其占据导致通道开放。
Large conductance calcium-activated K+ (K-Ca) 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 K-Ca 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 approximate to niflumic acid >> mefenamic acid. These results indicate that K-Ca channels possess at least one fenamatereceptor whose occupancy leads to channel opening.