NEGATIVE INOTROPIC MECHANISM OF ACETYLCHOLINE IN ISOLATED FROGS MYOCARDIUM

The question is examined on electrically stimulated frog ventricular strips whether acetylcholine exerts its negative inotropic effects in an exclusively indirect way, i.e. by an abbreviation of action potential or whether, in addition, a direct inhibitory action of acetylcholine on excitation-contraction coupling or on the contractile machinery itself has to be assumed. The results show that under the influence of acetylcholine a strict correlation between action potential duration and contraction amplitude is maintained over the whole range of concentrations tested (10-10 to 10-3 g/ml). This correlation is not affected by changes in stimulation frequency, temperature or extracellular Ca++ concentration. The observations on frog's myocardium indicate that the negative inotropic action of acetylcholine is exclusively due to the abbreviation of action potential. Accordingly, even in the presence of very high acetylcholine concentrations (1 mg/ml), the mechanical peak tension of frog ventricular strips does not decline if the contractile system is activated by repetitive tetanic stimuli or by membrane depolarization in an isotonic KCl solution. © 1968 Springer-Verlag.