Farley_1977_J.Pharmacol.Exp.Ther_201_199

The effects of acetylcholine (ACh) and K+ on tension and membrane potential were studied in order to determine the role of electromechanical and pharmacomechanical coupling in ACh-induced contractions of dog trachealis muscle. Potassium causes sustained contractions of the muscle via membrane depolarization, which appears to be related in a linear manner to the log of the external K+ concentration. From the K+ experiments a curve relating membrane potential and tension was obtained. The resting membrane potential of the trachealis is -30 +/- 1 mV. At a dose of 10(-7) M ACh the membrane is depolarized to about -55 mV and then at 10(-6) M ACh there is more depolarization to about -40 mV. At higher doses of drug there is no further change in membrane potential. The relationship between the dose of ACh and tension is much different. Contraction begins at 10(-7) M ACh but does not saturate until a dose of 10(-3) M is reached. The data were interpreted by using the relationship between EM and tension from the K+ experiments and the ACh dose-response curves as follows. At 10(-7) M ACh only pharmacomechanical coupling is involved in the contraction. At higher drug doses both pharmaco- and electromechanical coupling are involved, but pharmacomechanical coupling appears to play a much greater role. The maximal contribution of electromechanical coupling is approximately 30% of the contraction and this occurs at 10(-6) M ACh.