我們已知KCNQ4基因蛋白存在內耳毛細胞中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，AS-84，AS-77，PAP-10，PAP17a對於人類的KCNQ4
基因(與polymorphism)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。此電流會被鉀離子
阻斷劑linopirdine (0.25 mM) 所抑制。實驗發現某些補骨脂衍生物(psoralen derivatives)
具有抑制KCNQ4電流的作用，其中PAP-1與PAP17a 具有顯著的抑制作用。PAP-1 (30 M)
與PAP17a (30 M) 可分別抑制KCNQ4電流約50%與40%。AS-84，AS-77與PAP-10對於
KCNQ4電流並無顯著的抑制作用。PAP-1與PAP17a 對於KCNQ4 鉀離子電流電位依賴性
的二分之一活化電位無明顯偏移作用。PAP-1 與PAP17a 對於KCNQ4 的變異型
(F182L;V404I)與wild type比較並無顯著的差異。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PAP-1與PAP17a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 is expressed in inner and outer hair cells of the inner
ear and plays an important role for auditory transmission. In this study the effects of
psoralen derivatives, PAP-1, AS-84, AS-77, PAP-10 and PAP17a on the function of
KCNQ4 (and mutants) 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. This current was blocked
almost completely by 0.25 mM linopirdine, a selective blocker of KCNQ4 channel. These
experiments have shown that psoralen derivatives PAP-1 and PAP17a have inhibiting
effect on the KCNQ4 current. The inhibiting effect of KCNQ4 current about 50 % and
40% by treated with PAP-1 (30 M) and PAP17a (30 M) respectively. The other
psoralen derivatives AS-84, AS-77 and PAP-10 were no inhibiting effect of KCNQ4
current. Furthermore, PAP-1 and PAP17a did not produce a shifted effect of half-maximal
activation (V1/2) voltage. There are no difference in the inhibiting effect of KCNQ4 current
between the mutants (F182L and V404I) and wild type. The result reveals that psoralen
derivatives PAP-1 and PAP17a possess the effect on the inhibiting KCNQ4 channels. The
clinical implication of these observations is a need to further evaluation.
