AJP - Heart and Circulatory Physiology, Vol 252, Issue 4 807-H815, Copyright © 1987 by American Physiological Society
Positive inotropic effects of acetylcholine and BAY K 8644 in embryonic chick ventricle
Y. Tsuji, T. Tajima, J. Yuen and A. J. Pappano
BAY K 8644 augmented Ca2+-dependent action potentials and evoked a positive
inotropic effect in embryonic chick ventricle. These effects are consistent
with the properties of this Ca channel "agonist" whose actions are
independent of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent
phosphorylation. At low to intermediate concentrations (10(-8) to 10(-6)
M), the cholinergic agonists acetylcholine, carbachol, and oxotremorine
inhibit Ca2+-dependent action potentials and contractions in embryonic
ventricle only in the presence of drugs that cause cAMP accumulation. The
prediction that low to intermediate concentrations of these cholinergic
agonists should not inhibit the effects of BAY K 8644 on Ca2+-dependent
action potentials and contractions was borne out experimentally. This
result is consistent with the cAMP hypothesis for muscarinic inhibition. It
is noteworthy that all cholinergic agonists tested evoked a positive
inotropic effect at high concentrations (greater than 10(-6) M) in the
presence or absence of BAY K 8644. The positive inotropic effect was
initiated by muscarinic receptors for it was blocked by atropine and was
independent of endogenous catecholamines, since it occurred in the presence
of propranolol. It is speculated that the positive inotropic effect of
muscarinic agonists in embryonic heart muscle is related to stimulation of
phosphoinositide metabolism.
