内皮素和ATP敏感性钾通道介导缺氧所致家兔窦房结起搏细胞的电生理效应

ENDOTHELIN AND ATP-SENSITIVE POTASSIUM CHANNEL MEDIATE ELECTROPHYSIOLOGICAL CHANGES INDUCED BY HYPOXIA IN RABBIT SINOATRIAL NODE

用细胞内微电极技术研究了ＡＴＰ－敏感性钾（Ｋ_（ＡＴＰ））通道和内皮素（ｅｎｄｏｔｈｅｌｉｎ，ＥＴ）在缺氧所致窦房结起搏细胞负性频率中的作用，主要结果如下：（１）缺氧引起窦房结起搏细胞的ＲＰＦ降低和ＡＰＤ缩短，这一效应随时间延长而加重。（２）Ｋ_（ＡＴＰ）通道开放剂ｃｒｏｍａｋａｌｉｍ浓度依赖性地对窦房结起搏细胞有负性频率作用，且明显缩短ＡＰＤ_（５０）。该通道的阻断剂格列苯脲能部分阻断缺氧对起搏细胞的上述效应，表明缺氧效应中有Ｋ_（ＡＴＰ）通道的参与。（３）ＥＴ－１可显著加重缺氧所致的ＲＰＦ降低，使起搏细胞停跳时间前移；而以ＥＴ_Ａ受体阻断剂ＢＱ－１２３预处理窦房结标本后，则能有效地缓解缺氧对起搏细胞的效应，提示内源性ＥＴ－１的释放在缺氧效应中的作用。上述结果表明，缺氧所致起搏细胞的负性频率作用和ＡＰＤ缩短，与Ｋ_（ＡＴＰ）通道的激活和内源性ＥＴ－１的释放有关。

The role of ET and KATP channel in hypoxia-induced negative chronotropic effect of pacemaker cells in rabbit sinoatrial node was studied with intracellular microelectrode technique. The results obtained were as follows: (1 ) Hypoxia produced a progressive decrease in the velocity of diastolic depolarization (VDD) of pacemaker cells resulting in a reduced rate of pacemaker firing (RPF), and induced a decrease in APD, especially APD50. (2) KATP channel opener cromakalim markedly induced asiegative chronotropic effect in a concentration-dependent manner and significantly shortened APD50. KATP channel blocker glibenclamide alleviated the effects of hypoxia on pacemaker cells, thereby suggesting the involvement of KATP channel in the hypoxia-induced effects. (3) By super fusion of ET-1, the hypoxia-induced decrease in RPF was remarkably potentiatedand the occurrence of pacemaker arrest was shifted to an earlier time. The hypoxia-induced effects could be effectively attenuated after pretteatment with BQ-123, implying the role of endogenous ET-1 release in hypoxia-induced effects. It is concludedthat the negative chronotropic effect and the decrease in APD induced by hypoxia may be attributed to the activation of KATP channel and the release of endogenous ET.