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研究生(外文):Ming-Chi Jiang
論文名稱(外文):KMUP-1 inhibits L-type calciumchannels in rat basilar artery myocytes
外文關鍵詞:KMUP-1basilar artery myocytescalcium channels
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KMUP-1是一化學合成之嘌呤類衍生物。在先前研究發現,在大鼠胸主動脈血管平滑肌、兔子海綿體平滑肌及天竺鼠氣管平滑肌中, KMUP-1皆具有藉著增加環化核苷酸 (cyclic nucleotides)、鉀通道開啟活性及磷酸二酯酶 (PDE) 抑制作用而造成的鬆弛作用。然而,KMUP-1對於鈣離子電流的抑制作用尚未被直接研究證實過。
本實驗的主要目的為研究KMUP-1對於L-型鈣離子通道之作用。我們利用傳統全細胞膜電位箝制技術來研究於大鼠基底動脈平滑肌細胞上,通過 L-型鈣離子通道之鋇電流。於電位箝制狀態下, KMUP-1可濃度相關性地抑制鋇電流,但是不改變鋇電流之電流電位相關性。KMUP-1可抑制由蛋白質激酶C (PKC) 活化劑,phorbol 12-myristate 13-acetate (PMA, 1 ?嵱),所增加的鋇電流。前處理給予PKC抑制劑 chelerythrine (5 ?嵱),可增強KMUP-1抑制鋇電流之作用。然而前處理給予Rho kinase 抑制劑 Y-27632 (30 ?嵱) 則不顯著影響KMUP-1 抑制鋇電流之作用。配合細胞內鈣離子濃度測定,KMUP-1會抑制100 mM KCl及 1 ?嵱 PMA所誘發的細胞內鈣離子濃度增加。另外,KMUP-1也會抑制由10 ?嵱 Thapsigargine所誘發的細胞內鈣離子濃度增加。根據以上的結果,我們認為KMUP-1可濃度及電位相關性地抑制 L-型鈣離子通道,並且此抑制作用為和 PKC 路徑部分相關。
KMUP-1, a chemically synthetic xanthine-based derivative, has been demonstrated not only increase of cyclic nucleotides and inhibition of phosphodiesterases, but also activation of K+ channels resulting in relaxation in rat aortic smooth muscle (SM), rabbit corpus cavernosum and guinea-pig tracheal SM. However, a direct evidence of calcium currents inhibition by KMUP-1 has not yet been documented.
This study is to examine the effects of KMUP-1 on L-type calcium currents (ICa,L). We used the conventional whole cell patch-clamp technique to investigate Ba2+ currents (IBa) through L-type Ca2+ channels in rat basilar artery myocytes. Under voltage-clamp conditions, KMUP-1 inhibited the IBa in a concentration-dependent manner without any change in current-voltage relationship of IBa. Additionally, KMUP-1 inhibited the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA, 1 ?嵱), induced IBa. Pretreatment with the PKC inhibitor chelerythrine (5 ?嵱) enhances the inhibition of IBa by KMUP-1. However, a Rho kinase inhibitor Y-27632 (30 ?嵱) failed to affect the inhibition of IBa by KMUP-1. In fura-2-loaded rat basilar arteries, KMUP-1 inhibited the Ca2+ signal evoked by 100 mM KCl and 1 ?嵱 PMA. In addition, KMUP-1 also inhibited the Ca2+ signal evoked by 10 ?嵱 thapsigargine, a specific inhibitor of endoplasmic reticulum Ca2+-ATPase. In light of these results, we suggest that KMUP-1 inhibits the L-type calcium channels in concentration- and voltage-dependent manners in rat basilar artery myocytes and the effects may partially related to the PKC pathway.
英文摘要 2
中文摘要 3
緒論 5
實驗材料與方法 12
實驗結果 22
實驗討論 28
參考文獻 35
實驗圖表 48
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