Characterization of a biphasic response of the chronically denervated diaphragm of the rat to the same cholinergic agonist

1. The effects of acetylcholine (ACh) and carbaminoylcholine (carbachol) on the chronically denervated diaphragm of the rat were investigated quantitatively. 2. Both agonists evoke a biphasic mechanical response. An initial, rapid contraction is followed by a subsequent slow contracture. 3. The log dose-response curves of the initial response deviate at several points from theoretical curves based upon the law of mass action. The theoretical curves display a linear proportionality between stimulus and effect. The dose range covered by the experimental curve is reduced, the slope is steeper than that of the theoretical curves and the point of inflection is shifted to lower concentrations, evoking an asymmetry with regard to the 50%-value. These deviations can be accounted for, if the presence of a stimulus threshold (s) is assumed. The existence of such a stimulus threshold is to be expected in the case of the all-or-none response in striated muscle. The threshold amounts tos ∼ 55% for ACh ands ∼ 35% for carbachol (s as percentage of the maximal response). 4. In contrast, the dose-response curve of the second slow contracture, which is maintained over 15 min, agrees well with the theoretical curves; a stimulus threshold is not detectable. The dose-response curve approaches the ideal case of the linear function between receptor occupation, stimulus and effect.