PHARMACOLOGIC ISOLATION OF SINOATRIAL ACTIVITY FROM EFFECTS OF NEURAL EXCITATION BY USE OF TETRODOTOXIN

¹ Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan

Effect of tetrodotoxin was studied by selective administration into the sinus node artery of vagotomized dogs in vivo. A deceleration of the sinus rhythm was observed at doses between 0.1 and 1.0 µg, while sinus irregularity and finally atrioventricular nodal rhythm resulted from doses above 10 µg. The sinoatrial pacemaker fibers recovered their activity within about 30 minutes. Tetrodotoxin blocked the effect of electrical stimulation of either the right vagus or the right stellate ganglion without blocking the effects of norepinephrine or acetylcholine upon the sinus rate. The sinoatrial response to tyramine was not modified by tetrodotoxm treatment. These findings suggest that tetrodotoxin only blocks transmitter release caused by nerve excitation. Paradoxical chronotropic responses of the sinoatrial node, occasionally induced by administration of either acetylcholine or norepinephrine into the sinus node artery, were completely prevented by lower doses of tetrodotoxin, and the normal chronotropic responses to each of these substances was obtained as long as tetrodotoxin was effective.