AJP - Heart and Circulatory Physiology, Vol 256, Issue 4 1073-H1078, Copyright © 1989 by American Physiological Society
Muscarinic autoreceptors do not modulate kinetics of acetylcholine release in hearts
F. Dexter, Y. Rudy and M. N. Levy
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
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 less than 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.
