Effects of hirsutine and dihydrocorynantheine om the action potentials of sino-atrial node, atrium and ventricle

The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla MIQ , JACKSON with antihypertensive, negative chronotropic and antiarrhythmic a ctivity, and its C3 structural epimer, dihydrocorynantheine, on membrane po tentials of rabbit sino-atrial node and guinea-pig right ventricle and left atrium were studied with microelectrode techniques. In sino-atrial node pr eparations, hirsutine and dihydrocorynantheine (0.1 mu M to 10 mu M) concen tration-dependently increased cycle length, decreased slope of the pacemake r depolarization (phase 4 depolarization), decreased maximum rate of rise a nd prolonged action potential duration. In atrial and ventricular preparati ons, both compounds (0.1 mu M to 30 mu M) concentration-dependently decreas ed maximum rate of rise and prolonged action potential duration. These resu lts indicate that hirsutine and dihydrocorynantheine have direct effects on the action potential of cardiac muscle through inhibition of multiple ion channels, which may explain their negative chronotropic and antiarrhythmic activity.