ELECTROPHYSIOLOGICAL BASIS OF EXCITATION OF CANINE COLONIC CIRCULAR MUSCLE BY CHOLINERGIC AGENTS AND SUBSTANCE-P

Abstract

The circular muscle layer of the canine colon exhibits omnipresent rhythmic periodic waves of depolarization (slow waves), acting as pacemaker activity. The electrophysiological and motor responses of this layer to the muscarinic agonists acetylcholine and carbachol, and to the excitatory peptide substance P, were studied using the sucrose-gap technique. Changes in the contractile activity were examined in organ bath experiments. The slow waves consisted of an initial potential followed by a plateau potential. All substances depolarized the membrane and increased dramatically the duration of the plateau potential resulting in a decrease of the slow wave frequency. The amplitude of the plateau potential was often increased significantly. Carbachol and substance P readily evoked spiking activity, whereas acetylcholine did not. Both spiking activity and the plateau potential generated contractile activity. The prolongation of the slow wave duration caused a profound alteration of the pattern of contractions. Long-lasting tachyphylaxis to the effect of substance P, but not to acetylcholine or carbachol, occurred. The electrophysiological and motor effects of the drugs were due to a direct action on the smooth muscle cell membrane. This study provides an electrophysiological basis for prolonged circular muscle contractions of the colon, and it emphasizes the pacemaker activity of gastrointestinal smooth muscle as an important site of drug action.