多巴胺激活Kv通道抑制胰岛素分泌的电生理机制  

Study of electrophysiological mechanism of dopamine inhibiting insulin secretion by Kv channels

作　　者：薛欢 钟向琴 刘萌萌 路志红 温芝潼 崔丽娟 石晓媛 邢皓杰 赵昕 张语珊 章毅 XUE Huan;ZHONG Xiang-qin;LIU Meng-meng;LU Zhi-hong;WEN Zhi-tong;CUI Li-juan;SHI Xiao-yuan;XING Hao-jie;ZHAO Xin;ZHANG Yu-shan;ZHANG Yi(Dept of Pharmacology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院药理学教研室,山西太原030001

出　　处：《中国药理学通报》2022年第1期105-109,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81770776,81973378,82073909);山西省高等学校优秀成果培育项目(No 2019KJ022)。

摘　　要：目的探讨多巴胺激活电压依赖性钾(Kv)通道抑制葡萄糖刺激胰岛素分泌的电生理机制。方法分离雄性SD大鼠胰岛和β细胞,根据实验使用多巴胺(DA)、D;样受体激动剂(SKF38393)和D;样受体激动剂(Quinpirole)及阻断剂(Eticlopride)进行干预。酶联放射免疫实验测定胰岛素含量;膜片钳电压钳记录β细胞膜上Kv通道电流的变化,电流钳记录动作电位时程的长短;DiBAC4(3)染色观察INS-1细胞膜电位的变化。结果 SKF38393对胰岛素分泌和Kv通道均没有明显影响;Quinpirole明显抑制胰岛素分泌,并且增加Kv通道电流;多巴胺明显抑制胰岛素分泌,增加Kv通道电流,缩短β细胞动作电位时程,且均可被Eticlopride逆转;此外,多巴胺降低INS-1细胞膜电位。结论多巴胺作用于D;样受体,活化Kv通道,缩短动作电位时程,降低β细胞膜电位,从而发挥抑制葡萄糖促进胰岛素分泌的作用。Aim To study the electrophysiological mechanism of dopamine inhibiting insulin secretion by voltage-dependent potassium(Kv) channels. Methods Islets and β cells were isolated from male SD rats. D;-like receptor agonist(SKF38393), D;-like receptor agonist(Quinpirole) and antagonist(Epiclopride) were used according to the experiment. Insulin secretion was detected by insulin radioimmunoassay. Whole-cell patch-clamp technique was applied to detect Kv channel currents and action potential duration of β cells. DiBAC4(3) staining was used to observe membrane potential. Results SKF38393 did not affect insulin secretion and the Kv channel currents. Quinpirole significantly inhibited insulin secretion and increased Kv channel currents. Dopamine significantly inhibited insulin secretion, increased Kv channel currents and shortened action potential duration of β cells, which could be reversed by epiclopride. In addition, dopamine decreased membrane potential of INS-1 cells. Conclusions Dopamine inhibits insulin secretion by acting on D;-like receptors, resulting in actived Kv channels, shortened action potential duration and decreased cell membrane potential.

关 键 词：多巴胺 电压依赖性钾通道 动作电位时程 胰岛素分泌 D 样受体 全细胞膜片钳 

分 类 号：R-332[医药卫生] R322.57