Muscarinic autoreceptors do not modulate kinetics of acetylcholine release in hearts

We determined the time course of the cellular mechanism that mediates the attenuation of the chronotropic response in anesthetized dogs to decreases in the time interval (interpulse interval) between pulses of vagal stimuli. We injected propranolol, cut the cervical vagi, and repetitively stimulated the cardiac segment of the right vagus nerve with one brief burst of electrical pulses during each cardiac cycle. We recorded the initial and steady-state changes in cardiac cycle length that were induced by the phasic vagal stimulation. The decrease in the interpulse interval decreased the initial and steady-state responses. The time delay between the release of acetylcholine (ACh) from the vagal nerve endings in the heart and inhibition of the release of additional ACh was < 4 ms. Published delays between the time of ACh release and the time of the resulting change in membrane potential, in other biological systems, are 30-12,000 ms. We conclude that the time delay was too brief for muscarinic autoreceptors to have mediated the attenuation of ACh release from postganglionic vagal nerve endings in the heart in response to decreases in interpulse interval.