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| Title: | Multiple Cellular Electrophysiological Effects of a Novel Antiarrhythmic Furoquinoline Derivative Ha-7 N-Benzyl-7-Methoxy-2,3,4,9-Tetrahydrofuro 2 ,3-B Quinoline-3,4-Dione in Guinea Pig Cardiac Preparations |
| Authors: | 張國志;蘇銘嘉;郭盛助;林宗平;李英雄
CHANG, GWO-JYH;SU, MING-JAI;KUO, SHENG-CHU;LIN, TSUNG-PING;LEE, YING-SHIUNG |
| Contributors: | 藥理學科所 |
| Keywords: | RECTIFIER K+-CURRENT;VENTRICULAR MYOCYTES;D-SOTALOL;ATRIAL- FIBRILLATION;ACTION-POTENTIALS;2 COMPONENTS |
| Date: | 2006 |
| Issue Date: | 2009-09-23T08:31:41Z |
| Abstract: | We studied the electrophysiological and antiarrhythmic actions of HA-7 [ N-benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[ 2,3b] quinoline-3,4-dione], a furoquinoline alkaloid derivative, in guinea pig heart preparations. In the perfused whole heart model, HA-7 caused a prolongation in the basic cycle length, ventricular repolarization time, and the atrioventricular ( AV) nodal Wenckebach cycle length and prolonged the refractory period of the atrium, AV node, and His-Purkinje system. The atrioventricular conduction interval was also prolonged in a frequency-dependent manner. In isolated hearts, HA-7 significantly raised the threshold for experimental atrial fibrillation and reduced the occurrence of reperfusion-induced ventricular fibrillation. Conventional microelectrode-recording study shows that HA-7, but not d-sotalol, prolonged the action potential duration ( APD) and decreased the maximum rate of depolarization in isolated atrial strips. In ventricular papillary muscles, higher concentrations of HA-7 caused a prolongation of APD 90 in a frequency- independent manner, whereas d-sotalol exerted a reverse frequency- dependent action on this parameter. Whole-cell patch clamp results on ventricular myocytes indicate that HA-7 decreased both the slow ( I-Ks) ( IC50 = 4.8 mu M) and fast component ( I-Kr) ( IC50 = 1.1 mu M) of the delayed rectifier K+ currents. Similar results could also be observed in atrial myocytes. The inward rectifier K+ current ( I-K1) was also reduced somewhat by HA -7. HA-7 also suppressed the Na+ inward current ( I-Na) ( IC 50 = 2.9 mu M) and inhibited the L- type Ca2+ current ( I-Ca ) ( IC50 = 4.0 mu M, maximal inhibition =69%) to a lesser extent. We conclude that HA-7 blocks multiple ionic currents and that these changes affect the electrophysiological properties of the conduction system as well as the myocardial tissues and may contribute to its antiarrhythmic efficacy. |
| Relation: | JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS v.316 n.1 pp.380 -391 |
| Appears in Collections: | [藥理學科暨研究所] 期刊論文
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