夾竹桃麻素(aPO, 4'-hydroxy-3'-methoxyacetophenone)被認為是一種可滲透細胞的抗炎酚類化合物，可作為NADPH依賴性氧化酶(NOX)的抑製劑。然而，aPO直接與細胞膜離子通道相互作用以改變興奮性細胞中離子電流的幅度以及門控的機制仍不清楚。因此，我們試圖探索aPO對垂體細胞GH3中離子電流的任何修飾。在全細胞電流記錄中，發現GH3細胞暴露於aPO會刺激不同效力的電壓門控:峰值Na+電流(INa(T))和持續Na+電流(INa(P))。aPO在GH3細胞中峰值或持續INa的差異增加所需要的EC50值估計分別為13.2及2.8μM，而其在電流失活的緩慢組分中延遲所需的KD值為3.4 μM。在細胞暴露於aPO(10 μM)期間，INa的電流-電壓關係略微向負電位轉移；然而，電流的穩態失活曲線在aPO(10 μM)存在時向右移動。在10 μM aPO存在下，峰值INa失活狀態的恢復速度增加。在aPO持續存在的情況下，進一步應用rufinamide或ranolazine有效地逆轉了aPO刺激增加的INa。在methylglyoxal或superoxide dismutase預處理的細胞中，aPO對峰值INa的刺激作用仍然有效。通過使用不同持續時間的直立等腰三角形斜坡脈衝，aPO的存在增強了在低閾值或高閾值測量的持續INa的幅度，同時在低閾值或高閾值出現的電壓依賴性遲滯現象(Hys(V))強度增加。同樣，在HL-1小鼠心肌細胞中，aPO的存在增加了INa的峰值幅度，並降低了電流的失活率及去活化率，並且進一步添加ranolazine或esaxerenone可逆轉aPO增強的INa。連同這些數據，本研究提供了一個重要但尚未確定的發現，該發現表明，儘aPO可有效抑制NOX活性，但aPO可能直接且協同地擾亂電興奮性細胞中INa的幅度、門控和Hys(V)。

Apocynin (aPO, 4’-hydroxy-3’-methoxyacetophenone) has been viewed as a cell-permeable, anti-inflammatory phenolic compound which can act as an inhibitor of NADPH-dependent oxidase (NOX). However, the mechanisms through which aPO can interact directly with membrane ion channels to modify the amplitude or gating of ionic currents in excitable cells is unclear. Hence, we intended to assess any modifications of aPO on ionic currents present in pituitary GH3 cells. In whole-cell current recordings, GH3-cell exposure to aPO was found to enhance the peak and late components of voltage-gated Na+ current (INa) with different potencies. The EC50 value of aPO needed for its differential increase in peak or persistent INa in GH3 cells was calculated to be 13.2 or 2.8 μM, respectively, while the KD value required for its retardation in the slow component of current inactivation was estimated as 3.4 μM. The current versus voltage relation of INa was shifted slightly to more negative potential during cell exposure to aPO (10 μM); however, the steady-state inactivation curve of the current was shifted in a rightward direction in its presence. Recovery of peak INa inactivation was elevated in the presence of 10 μM aPO. In continued exposure to aPO, further application of rufinamide or ranolazine reversed aPO-stimulated INa effectively. In cells incubated with methylglyoxal or superoxide dismutase, the stimulatory effect of aPO on peak INa remained unaltered. By using an upright isosceles-triangular ramp pulse of varying duration, the amplitude of persistent INa measured at low or high threshold was enhanced by the aPO presence, along with increased strength of voltage-dependent hysteresis (Hys(V)) appearing at low or high threshold. Likewise, in HL-1 murine cardiomyocytes, the aPO presence increased the peak amplitude of INa as well as decreased the inactivation or deactivation rate of the current, and further addition of ranolazine or esaxerenone reversed aPO-accentuated INa. Altogether with these data, the present study provides an important yet unidentified finding revealing that, notwithstanding its effectiveness in suppressing NOX activity, aPO may directly and concertedly perturb the amplitude, gating kinetics, and Hys(V) strength of INa residing in different types of electrically excitable cells.

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