Isotonic and isometric responses of different tonic muscles to agonists and antagonists.

1 With isotonic recording the percentage of muscle shortening as compared with the maximal possible shortening, and with isometric recording the percentage of developed tension were determined. In relatively 'thick' muscles, such as dorsal leech muscle, frog rectus abdominis or protractor pharynx of holothuria (0.3-0.8 mm thick), the concentrations of a full agonist (carbachol) producing a given percentage of tension, (e.g. 50%) are about 5 times greater than the concentrations, producing the same percentage of shortening. In 'thin' muscles the difference between the percentage of shortening and tension is either small (retractor dentis of the sea urchin, 0.1 mm thick, response to carbachol) or absent (guinea-pig ileum, 0.06 mm thick, responses to methylfurmethide). The possible mechanism underlying this difference is discussed. 2 With partial agonists (dodecamethonium and heptamethonium) the fractional tension of the frog rectus abdominis is always less than the fractional shortening and the correlation between shortening and tension is the same as in the case of full agonists. 3 The blocking activity of (+)-tubocurarine on the frog rectus abdominis is the same in isotonic and in isometric conditions. 4 On the frog rectus abdominis the alkylating agent, decamethonium mustard, does not produce any 'parallel shift' of the dose-response curve for carbachol, the only result of alkylation being a decrease in maximal response, which is more pronounced in isometric than in isotonic conditions. The degree of decrease is in accordance with the correlation between percentage of shortening and percentage of tension in the absence of alkylating agent. Probably this muscle does not possess any 'spare receptors'. 5 On the frog muscle the dose-isometric response curve for acetylcholine (ACh) is shifted toward greater concentration about 33-fold as compared with the dose-isotonic response curve but after the inhibition of cholinesterases the shift is only about 6-fold. The same shift (5-fold) is observed for carbachol, which is not hydrolysed by cholinesterases. The results with ACh are due to the fact, that after cholinesterase inhibition the sensitivity to ACh increases in isotonic conditions only 13-fold, but in isometric conditions it increases 71-fold. Probably under isometric conditions, when the muscle remains in the extended state, the rate of hydrolysis of ACh is much greater than under isotonic conditions when the muscle is shortened during contraction.