Desensitization of smooth muscle cells in the guinea pig taenia coli to prolonged application of carbachol.

Abstract

To investigate the mechanism of desensitization to carbachol (Carb) in smooth muscle, the effects of prolonged applications of Carb on the electrical and mechanical properties of the guinea pig taenia coli were examined by either the microelectrode method or the double sucrose gap method.1. Prolonged application of Carb (10-5 g/ml; 5.5×10-5 M) initially depolarized the membrane, reduced the membrane resistance and evoked contracture. These responses did not, however, continue but a desensitization to Carb then developed, i. e. the membrane was gradually repolarized, membrane resistance increased, and the muscle relaxed in spite of the presence of Carb.2. During the repolarization phase in the presence of Carb (10-5 g/ml), repeated current pulses transiently produced larger electrotonic potentials than those expected from the electrical displacement of the membrane potential. This transient increase of the membrane resistance was not directly related to the desensitization and it might be accounted for by a reduction of K permeability in the extrareceptor region at the depolarized condition.3. Desensitization was accelerated in modified Krebs solutions with reduced Na or excess Ca, but was suppressed in solutions either with reduced Ca, or with reduced Cl or with excess K.4. Procaine (27×10-5 g/ml; 1 mM) supPressed both the depolarization and the desensitization induced by Carb. Hypertonic Krebs solution also suppressed the action of Carb on the taenia coli.5. The contrast between the actions of Carb on the taenia coli and frog motor endplate has been discussed in terms of the ionic mechanisms involved.