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Single-pulse stimulation of the vagus nerve in turtles (Pseudymys floridana) produced the well-known negative inotropic effect on the atria. After stimulation, the peak amplitudes of the atrial contractions exhibited an envelope which appeared to be proportional to the concentration of acetylcholine at the receptor sites. Postulating a quantized release of acetylcholine with each stimulus, the envelope was modeled by a two-equal-compartment configuration. In about 63% of the cases this envelope behaved as if it described a critically damped system, in 18% of the cases it behaved as if the system were slightly overdamped, and in the remaining 19% it corresponded to a lightly underdamped system. The average washout time constant per compartment calculated from the single-pulse response was 4.7 ± 0.8 seconds (SD). Repetitive stimulation was provisionally equated with a constant release of acetylcholine; its mathematical description was derived from the time integral of the single-pulse case, i.e., from a direct application of indicator-dilution theory. However, the average time constant obtained from this second type of fit was only 0.84 ± 0.4 seconds. This lower value was interpreted as a dynamic modification (perhaps nonlinear) due to accumulation of acetylcholine and probably associated with an increase in acetylcholine esterase activity.

A Two-Compartment Model Describing the Release and Negative Inotropic Action of Acetylcholine on the Heart