Potentiating effects of 4-aminopyridine on responses to intramural vagal stimulation in the isolated dog atrium.

The effects of 4-aminopyridine (4-AP) on the chronotropic and inotropic responses to intramural parasympathetic nerve stimulation and to injection of acetylcholine (ACh) into the sinus node artery were investigated after treatment with propranolol in the isolated, blood-perfused dog atrium. 4-AP (3-100 micrograms) induced positive chronotropic and inotropic effects and 300 micrograms of 4-AP induced biphasic, negative and positive effects. The negative responses to 4-AP were completely blocked by 10 micrograms of atropine. 4-AP (more than 30 micrograms) potentiated significantly the negative chronotropic and inotropic responses to intramural parasympathetic nerve stimulation at a frequency of 3-30 Hz. The potentiation of the responses to stimulation was greater at a low than at a high frequency of stimulation. Potentiation of the chronotropic effect was greater than that of the inotropic one. 4-AP in the doses used did not change the negative chronotropic and inotropic responses to injection of ACh into the sinus node artery. These results suggest that the potentiation by 4-AP of the cardiac responses to parasympathetic nerve stimulation was due to an increase in release of ACh from nerve terminals but not to an increase in responsiveness at the effector site.