在胰臟β細胞中，ATP敏感鉀通道 (KATP) 由4個SUR1和4個Kir6.2亞基形成八聚體複合物，且受細胞內ATP與ADP的濃度所調控。 KATP通道的關閉誘導膜電位去極化，引起電位調控之鈣離子通道打開使鈣離子流入細胞內，繼而刺激胰島素分泌。 KATP通道功能的缺陷導致嬰兒持續性高胰島素血症性低血糖症（PHHI）。二氮嗪是PHHI患者的第一線治療方法。不幸的是，PHHI的新生兒形式中有90％對二氮嗪有抗藥性，而嚴重的PHHI患者通常需要進行部分胰腺切除手術。卡馬西平是一種抗癲癇藥，可糾正先天性高胰島素血症中SUR1突變引起的細胞膜表現量缺陷。 A28V是KCNJ11中的一種新型突變，其編碼Kir6.2亞基蛋白導致PHHI。 我們探討了卡馬西平和格列本脲是否可以挽救A28V Kir6.2突變造成的KATP 通道於細胞膜表現量的不足。用野生型（SUR1 / Kir6.2）或突變型（SUR1 / A28V Kir6.2）KATP通道轉染HEK293細胞，並且進行格列苯脲或卡馬西平處理。通過表面生物素化，格列本脲和卡馬西平增加了SUR1 / A28V Kir6.2轉染細胞中SUR1於細胞膜表達量。我們還用野生型或突變體Kir6.2在HEK293細胞中轉染了HA標記的SUR1。在格列本脲或卡馬西平處理後偵測了細胞膜表面HA的訊號，我們觀察到HA訊號在突變轉染細胞中免疫熒光染色增加。接下來，我們通過qPCR分析檢查了突變KATP通道是否增加了未折疊的蛋白應答（UPR），數據顯示卡馬西平對拯救突變KATP通道的影響不會影響參與UPR和SUR1的核糖核酸轉錄。同時，我們檢查了卡馬西平治療前後突變KATP通道的分佈。突變的KATP通道主要出現在高爾基體中。卡馬西平治療後，突變的KATP通道與高爾基體標記的共定位較少，並且通過進行免疫熒光染色在質膜上顯示出較強的訊號。免疫共沉澱結果也應證此現象。另外，我們也發現卡馬西平能減少突變KATP通道與溶體的共定位。我們亦檢視了卡馬西平如何調控溶體介導的自噬途徑，發現卡馬西平能啟動自噬反應但無法完成最後降解物質的步驟。總結來說，我們證明了卡馬西平處理透過協助突變KATP通道從高爾基體中拯救出來以及防止降解而使突變KATP通道運輸到細胞膜表面。

In pancreatic β-cells, ATP sensitive potassium channel (KATP), the octamer complex containing 4 SUR1 and 4 Kir6.2 subunits, is gated by the cellular (Arakel et al.) and [ADP], and the closure of KATP channels induces membrane depolarization followed by Ca2+ influx through voltage-gated calcium channel, which in turn stimulates insulin secretion upon glucose elevation. The loss function of KATP channel results in persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Diazoxide is the first line of treatment for patients with PHHI. Unfortunately, 90% of the neonatal forms of PHHI are resistant to diazoxide, and severe PHHI usually requires near-total pancreatectomy. Carbamazepine, an anti-epileptic drug, corrects the surface expression defects caused by a subset of SUR1 mutations in congenital hyperinsulinism. Importantly, the combination of diazoxide and carbamazepine led to enhanced mutant channel function. A28V is a novel mutation in KCNJ11 encodes Kir6.2 leads to PHHI. We investigated if carbamazepine and glibenclamide rescue forward trafficking deficit of A28V Kir6.2 mutation. HEK293 cells were transfected with either wildtype (SUR1/Kir6.2) or mutant (SUR1/A28V Kir6.2) KATP channels followed by glibenclamide or carbamazepine treatment. Carbamazepine increased total and surface expression of SUR1 in SUR1/A28V Kir6.2 transfected cells by surface biotinylation. We also transfected HA-tagged SUR1 with wildtype or mutant Kir6.2 in HEK293 cells, followed by surface HA staining after glibenclamide or carbamazepine treatment. We observed increased immunofluorescent staining in transfected mutant cells using an anti-HA antibody. Next, we checked if mutant KATP channels elevated the unfolded protein response (UPR) and the data showed that effects of carbamazepine on rescuing mutant KATP channels did not affect signaling molecules involved in the UPR and SUR1 using qPCR analysis. In the meantime, we examined the distribution of mutant KATP channels before and after carbamazepine treatment. Mutant KATP channels were presented mainly in the Golgi apparatus and lysosome. Upon carbamazepine treatment, mutant KATP channels showed less colocalization with the Golgi marker, GM130, and displayed intense staining in the plasma membrane by performing immunofluorescent staining; the co-IP results also correspond to the staining pattern. We also found that carbamazepine could reverse the colocalized pattern with lysome marker, LAMP1. For degradation system, western blotting data showed carbamazepine initiated autophagy through mTOR dependent pathway. Howerever, carbamazepine could not complete the autophagy flux. Collectively, we demonstrate that mutant KATP channels are rescued to the surface by carbamazepine treatment via assisting mutant KATP channels in exiting from GM130 and preventing lysosomal degradation.

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