Cholinergic mechanisms in heart: interactions with 4-aminopyridine.

Acetylcholine (ACh) hyperpolarized the guinea-pig atrium and increased the maximum rate of rise of the spike and ionic conductance. There was a dose-dependent decrease in action potential duration in most preparations. However, some atrial showed a contractility decrease without a concomitant change in action potential duration. This was not related to acetylcholinesterase activity. Reduction in contractility by ACh resulted from doses 10 times lower than were required for action potential shortening. Small quantitative differences in electrical response were seen between the left and right atria. 4-Aminopyridine lengthened the action potential and increased spike amplitude. These effects were not frequency-dependent but were potentiated by low Ko+. This drug antagonized both the electrical and contractile effects of ACh, suggesting that they are mediated by an increase in KO+ permeability. Modification of excitation-contraction coupling by ACh is discussed and a role for cyclic guanosine 3':5'-monophosphate suggested.