已知KCNQ4基因蛋白對於聽覺傳訊過程扮演著重要的角色。本實驗主要是研究補骨脂衍生物(PAP-1)與磷酸化脢抑制劑對於人類的KCNQ4基因的功能的影響。人類KCNQ4基因純化之cRNA打入爪蟾卵母細胞並於打入後2-4天的期間以雙電極電壓鉗定技術記錄其所表現的電流。補骨脂衍生物(psoralen derivatives)具有抑制KCNQ4電流的作用,所測得的KCNQ4鉀離子電流顯示是電位依賴性的其二分之一活化電位向右偏移,此電流會被鉀離子阻斷劑linopirdine (0.25 mM)所抑制。給予phosphatase 抑制劑okadaic acidand calyculin A (3 .mu.M)亦具有對KCNQ4相似的作用,會抑制KCNQ4鉀電流並使其二分之一活化電位曲線圖向左偏移分別是。Psoralen衍生物或phosphatase抑制劑對於未表現有KCNQ4爪蟾卵母細胞之內源性電流不具有影響性。Psoralen衍生物對於KCNQ4電流之調控是否經由phosphatase仍須進一步的證實。因此我們認為KCNQ4鉀電流可以被Psoralen衍生物所抑制,而在臨床上的作用須待進一步的評估。
It is has been known that KCNQ4 plays an important role for auditory transmission. In this study the effects of psoralen derivatives and phosphatase inhibitor on the function of KCNQ4 were investigated. The human potassium channel KCNQ4, expressed in the Xenopus oocytes injected with KCNQ4 cRNA and currents were recorded using the two-electrode voltage clamp technique. The psoralen derivatives have inhibiting effect on the KCNQ4 current, the expressed current showed the typical KCNQ4 voltage-dependence, with a voltage for half-maximal activation (V1╱2) shifted to right, and was blocked almost completely by 0.25 mM linopirdine, a selective blocker of KCNQ4 current. Application of phosphatase inhibitors, okadaic acid (0.5 .mu.M) or calyculin A (3 .mu.M) have the similar effect with psoralen derivatives on the KCNQ4 current, shifted V1╱2 to the right. Either psoralen derivatives or phosphatase inhibitors have no effect on the endogenous current of oocytes. If the effect of psoralen derivatives on KCNQ4 by the phosphatase activities needs to further investigate. The result reveals that psoralen derivatives possess the effect on the inhibiting KCNQ4 channels.