本文選題：辣椒素　切入點：HERG　出處：《武漢科技大學》2009年碩士論文

【摘要】： 目的:研究辣椒素對野生型及突變型HERG離子通道的阻斷作用,并試圖探尋發(fā)生在S6結構域的突變位點是否是辣椒素與HERG結合的重要作用位點。 方法:采用雙電極電壓鉗技術測定表達在非洲爪蟾卵母細胞上的HERG離子通道電流(野生型,Y652A型,F656A型)。 結果:辣椒素以濃度依賴性的方式阻斷野生型HERG鉀通道電流,其半最大效應濃度IC50為17.45μM。辣椒素的阻斷作用不改變野生型HERG通道50%最大激活時的電位,但使穩(wěn)態(tài)失活曲線向負值漂移。辣椒素可阻斷關閉和開放兩種狀態(tài)的HERG通道。然而,同野生型HERG通道的阻斷相比,Y652氨基酸殘基突變?yōu)楸彼岷笃渥钄嘧饔妹黠@增強,其IC50為5.68μM,而F656A突變與野生型的阻斷效應之間沒有明顯的差別。同時我們還發(fā)現(xiàn),使用25μM辣椒素后,Y652A型通道的穩(wěn)態(tài)激活向正向漂移5mV,而失活參數(shù)向負值增大的方向漂移-29mV。 結論:辣椒素結合并阻斷關閉及開放狀態(tài)的HERG通道,位于S6結構域的Y652是通道與辣椒素結合的重要位點。辣椒素對Y652A突變型HERG通道的阻斷作用明顯強于野生型,提示通道基因突變可能造成臨床上有些患者對辣椒素特別敏感。
[Abstract]:Aim: to study the blocking effect of capsaicin on wild and mutant HERG ion channels and to explore whether the mutation site in S6 domain is an important binding site of capsaicin to HERG. Methods: double electrode voltage clamp technique was used to determine the current of HERG ion channel expressed on Xenopus oocytes. Results: capsaicin blocked the wild-type HERG potassium channel current in a concentration-dependent manner, and its half-maximum effect concentration IC50 was 17.45 渭 M. the blocking effect of capsaicin did not change the potential of the wild-type HERG channel at 50% maximum activation. But the steady-state inactivation curve was shifted to a negative value. Capsaicin could block both closed and open HERG channels. However, compared with the blocking of wild-type HERG channels, the blocking effect of Y652 amino acid residues mutated to alanine was significantly enhanced. The IC50 was 5.68 渭 m, but there was no significant difference between the F656A mutation and the blocking effect of wild type. We also found that the steady-state activation of Y652A channel with 25 渭 M capsaicin drifted forward by 5mV, and the inactivation parameter drifted negative by -29mV. Conclusion: capsaicin binds and blocks the closed and open HERG channels. Y652 located in the S6 domain is an important site for the binding of capsaicin to capsaicin. The blocking effect of capsaicin on Y652A mutant HERG channel is stronger than that of wild type. This suggests that mutations in the channel gene may cause some patients to be particularly sensitive to capsaicin.
【學位授予單位】：武漢科技大學
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R33

【參考文獻】

相關期刊論文 前1條

1 ;Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain[J];Acta Pharmacologica Sinica;2007年07期

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本文編號：1697357