Cholinergic effect of 4-aminopyridine and adrenergic effect of 4-methyl-2-aminopyridine in cardiac muscle.

The effect of 4-aminopyridine (4AP) and 4-methyl-2-aminopyridine (4M2AP), 10(-3) M, was studied on isolated spontaneously beating right atria and electrically driven left atria of the rabbit and the cat. In the rabbit preparations, 4AP had a positive inotropic effect which was unaffected by propranolol or atropine, and a negative chronotropic effect which was abolished by atropine. In the cat, 4AP decreased both force and rate, and these effects were reversed when 4AP was repeated in the presence of atropine. In contrast, 4M2AP increased the rate and force of contraction in both species. These effects were reduced but not abolished when 4M2AP was repeated in the presence of propranolol. It is concluded that 4AP has a cholinergic effect presumably mediated by acetylcholine release which predominates over its direct positive inotropic effect in the rabbit but not in the cat, and which is responsible for its effect on rate in both species. 4M2AP also has a direct positive inotropic action, but its marked effects on force and rate of contraction are largely due to noradrenaline release. The selectivity of 4AP for cholinergic and 4M2AP for noradrenergic transmission suggests that there are differences in potassium channels or in calcium uptake or release mechanisms in the respective nerve terminals.