Role of acetylcholine in induction of repetitive activity in human atrial fibers.

The actions of acetylcholine and its interactions with epinephrine were studied in human atrial tissues by recording transmembrane potentials and contractile force. Acetylcholine (0.55-5.5 microM) reduced force, shortened the duration and shifted to more negative values the plateau of action potentials, abolished phase 4 depolarization, and suppressed the activity of spontaneous fibers. During the recovery, often there was a rebound increase in some parameters of the action potential and in force. Epinephrine (0.3-2.8 microM) induced oscillatory potentials and aftercontractions and acetylcholine abolished them. However, during the washout of acetylcholine in the presence of epinephrine, the oscillatory potentials and aftercontractions were larger than before acetylcholine, and repetitive activity was often induced. The inhibitory and excitatory effects of acetylcholine were mimicked by methacholine (5.1 microM) and abolished by atropine (1.5 microM). The postacetylcholine rebound was also potentiated by theophylline (0.6-2 mM) but was not blocked by propranolol (1-3.4 microM), prazosin (1 microM), and diltiazem (0.1 microM). It is concluded that in human atrial fibers acetylcholine has inhibitory as well as excitatory effects that are exaggerated in the presence of epinephrine and are mediated by the activation of the muscarinic receptor. The interaction between acetylcholine and epinephrine involves an antagonism at an intracellular level.