M 受体阻断剂对粉防己碱心肌负性肌力作用的调节及其离子机理

研究Ｍ 受体阻断剂对粉防己碱（Ｔｅｔ）负性肌力作用的影响并探讨其机理．记录Ｔｅｔ对豚鼠离体左心房收缩力，兔心房肌细胞动作电位及豚鼠单个心室肌细胞Ｃａ２＋ ，Ｋ＋ 通道电流的作用及Ｍ 受体阻断剂的影响．Ｍ 受体阻断剂阿托品（０．０３ μｍ ｏｌ·Ｌ－ １）及Ｍ２ 受体亚型阻断剂ＡＦ－ＤＸ １１６（１．０ μｍ ｏｌ·Ｌ－ １）能使Ｔｅｔ负性肌力作用的量效曲线平行右移， ＥＣ５０（μｍ ｏｌ·Ｌ－ １）由２８．９±０．９ 分别增至１２５±２１ 和１２７±１３；Ｔｅｔ（１－ １００ μｍ ｏｌ·Ｌ－ １）浓度依赖性缩短兔心房肌细胞动作电位时程ＡＰＤ２０，ＡＰＤ５０， 此作用被阿托品（０．０３ μｍ ｏｌ·Ｌ－ １）部分拮抗，而Ｔｅｔ延长ＡＰＤ９０ 的作用不受阿托品的影响．阿托品（１μｍ ｏｌ·Ｌ－ １）部分拮抗Ｔｅｔ（３０ μｍ ｏｌ·Ｌ－ １）对豚鼠心室肌细胞Ｌ－型钙电流的阻滞作用，而不影响其抑制内向整流钾电流（ＩＫ１）的作用． １ μｍ ｏｌ·Ｌ－ １乙酰胆碱则能逆转Ｔｅｔ对ＩＫ１的抑制．Ｍ 受体阻断剂对Ｔｅｔ阻滞钙通道作用的影响可能是其拮抗Ｔｅｔ负性肌力作用的主要离子机理．

Modulation by muscarinic receptor antagonists on negative inotropic effect of tetrandrine and its ionic mechanism 1

Influence of muscarinic acetylcholine receptor(mAChR) antagonists on negative inotropic effects of tetrandrine(Tet) was studied. In isolated guinea pig left atrium, atropine(0.03 μmol·L -1 ) and AF DX 116(1 μmol·L -1 ) markedly inhibited Tet decreasing contracting force, EC 50 (μmol·L -1 ) value was changed from 28.9±0.9 to 125±21 and 127±13 respectively. Atropine (0.03 μmol·L -1 ) partially antagonized shortening effects of Tet on APD 20 and APD 50 in rabbit right atrium, but did not affect prolongation of APD 90 in high concentration of Tet. Using whole cell patch clamp to record L type calcium current (I Ca L ) and inwardly rectifier potassium current (I K1 ) in single isolated ventricle cells of guinea pig, it was found that the inhibitory effect of Tet (30 μmol·L -1 ) on I Ca L was partially antagonized by atropine (1 μmol·L -1 ). The inhibitory effect of Tet (30 μmol·L -1 ) on I K1 was not affected by atropine (1 μmol·L -1 ), while reversed by acetylcholine (1 μmol·L -1 ). The results suggest that modulation of mAChR antagonists on calcium channel blocking effects of Tet is its main ionic mechanism in attenuating negative effects of Tet.