氯尼辛对心脏起搏细胞电活动的影响。

Effects of clonixin on the electrical activity of cardiac pacemaker cells.

Morales M A, Inostroza L, Salazar T, Paeile C

Department of Pharmacology, Faculty of Medicine, University of Chile, Santiago.

Gen Pharmacol. 1992 May;23(3):515-21. doi: 10.1016/0306-3623(92)90121-y.

Abstract

The electrophysiological effects of clonixin, a non-steroidal analgesic, on cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied by intracellular recording of transmembrane potentials. 2. Results show that clonixin (Clx) between 1 x 10(-6) M and 3 x 10(-4) M, decreases the OS, APA, Vmax and frequency of primary and subsidiary cells, however pacemaker cells differ in their sensitivity to Clx. 3. At 2 x 10(-6) M, Clx completely blocked the spontaneous beating of primary cells. It is necessary to increase the Clx concentration about two orders of magnitude in order to attain a similar degree of blockade of subsidiary cells. 4. Previous or simultaneous superfusion with atropine does not modify Clx effects, thus a probable cholinergic mechanism of action for Clx is discarded. 5. When Clx concentrations were lower than 5 x 10(-4) M, their effects on both types of cells were partially reversed by a 100% increase of external calcium concentration. 6. BAY K-8644 which stimulates calcium influx through calcium L-type channels, reverted Clx effects on pacemaker cells. 7. It is suggested that Clx blocks calcium inward current which generates all or part of the upstroke of primary cells and subsidiary ones, respectively.

摘要

采用跨膜电位细胞内记录法，研究了非甾体类镇痛药氯尼辛对自发搏动的青蛙窦房结心脏起搏细胞的电生理效应。2. 结果表明，1×10⁻⁶ M至3×10⁻⁴ M之间的氯尼辛（Clx）可降低主细胞和副细胞的动作电位时限（OS）、动作电位幅度（APA）、最大上升速率（Vmax）和频率，然而起搏细胞对Clx的敏感性有所不同。3. 在2×10⁻⁶ M时，Clx完全阻断了主细胞的自发搏动。要使副细胞达到类似程度的阻断，必须将Clx浓度提高约两个数量级。4. 预先或同时用阿托品灌注不会改变Clx的作用，因此排除了Clx可能的胆碱能作用机制。5. 当Clx浓度低于5×10⁻⁴ M时，外部钙浓度增加100%可部分逆转其对两种细胞的作用。6. 刺激钙通过L型钙通道内流的BAY K - 8644可逆转Clx对起搏细胞的作用。7. 提示Clx阻断分别产生主细胞和副细胞全部或部分上升支的钙内向电流。