Effects of guan-fu base A on spontaneous rate of isolated sinoatrial node of guinea pig

Guan-fu base A (GFA) is a new alkaloid isolated from the tuber of Aconitum coreanum in our institute. Its effects on spontaneous electrical discharge rate of intact sinoatrial node preparations were investigated. Unipolar Ag-AgCl2 electrodes and DC-amplification were used to record unipolar electrograms from the endocardial surface of the isolated right guinea pig atria. GFA (4.29-214.5 micrograms/ml) decreased the spontaneous electrical discharge rate of sinoatrial node in a dose-dependent manner. The most effective concentration (214.5 micrograms/ml) of GFA resulted in sinus rate of 115 +/- 8 bpm (n = 7, control rate 208 +/- 13 bpm) within 30 min. Low external Ca2+ (0.18 mmol/L) enhanced the rate in lowering effect of GFA, in contrast with high external K+ (10.8 mmol/L) diminishing the effect of GFA. The ratios of IC30 of negative inotropic effects over IC30 of negative chronotropic effects were 9.38 for GFA and 1.73 for verapamil. GFA antagonized the positive chronotropic effect of isoproperenol but did not antagonize the positive inotropic effect of isoproterenol. The consequence of lowering sinus rate by GFA was not interfered by propranolol (0.15 micrograms/ml) or atropine (0.05 micrograms/ml). These results suggest that the bradycardia by GFA is a direct effect on sinoatrial node, but not due to the calcium channel block or beta adrenoceptor block.