AJP - Heart and Circulatory Physiology, Vol 249, Issue 4 735-H740, Copyright © 1985 by American Physiological Society
Positive inotropic effect of acetylcholine in canine cardiac Purkinje fibers
R. F. Gilmour Jr and D. P. Zipes
The purpose of this study was to investigate possible mechanisms to explain
the positive inotropic effects of acetylcholine in canine cardiac Purkinje
fibers. Action potentials and tension were recorded from Purkinje fibers in
vitro using microelectrodes and a force transducer. Acetylcholine (10(-9)
to 10(-4) M) produced a dose-dependent increase in tension that was blocked
by atropine but not by propranolol, phentolamine, hexamethonium, or
verapamil. At 10(-5) and 10(-4) M, acetylcholine increased action potential
duration at 50% of repolarization (APD50) but did not affect resting
membrane potential, action potential amplitude, Vmax, or action potential
duration at 90% of repolarization (APD90). Isoproterenol (10(-7) M)
shortened APD50 and APD90 and increased developed tension. Subsequent
addition of acetylcholine (10(-5) M) prolonged APD50 and APD90 and
decreased tension. Increasing extracellular Ca2+ concentration [( Ca2+]o)
from 2.0 to 3.0 mM increased tension and shortened APD50. Addition of
acetylcholine (10(-5) M) increased tension further and prolonged APD50. In
K+-depolarized fibers high concentrations of acetylcholine (10(-4) M)
restored excitability, but lower concentrations (10(-6) M) suppressed slow
responses induced by isoproterenol. Thus acetylcholine alone or with
elevated [Ca2+]o increased APD50 and tension and facilitated the induction
of slow responses, yet in the presence of isoproterenol acetylcholine
increased APD50, decreased tension, and suppressed slow responses. These
effects were mediated by muscarinic receptors and were independent of
catecholamine release.
