Acetylcholine and Calcium on Membrane Permeability and Contraction of Intestinal Smooth Muscle

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Abstract
Acetylcholine elecited a sustained contraction and an increase in potassium efflux in longitudinal muscle isolated from the guinea pig ileum. Stepwise increases in the calcium concentration of the bathing medium from 0.06 to 36 mM generally reduced the increase in K efflux, but had a complex effect on the mechanical response. Contractions produced by high levels of acetylcholine became progressively larger or remained at a high magnitude as the Ca concentration was increased. Contractions produced by low levels of acetylcholine also improved initially, but were depressed again by the highest concentration of Ca introduced. Ethanol, in the appropriate concentration, inhibited completely the acetylcholine-induced contraction without reducing the increase in K efflux. Ca reversed this effect. Both extracellular Ca and ethanol depressed the large, transient increase in muscle tone developed by fibers that were preincubated in a high Ca medium and then exposed to a Ca free medium. These findings suggested that extracellular Ca ions react with 2 different sites in the membrane, a stabilizing site and a storage site. A muscle contraction is activated by Ca ions which diffuse from the storage site to the myoplasm. Ca ions reacting with the stabilizing site impede this diffusion process. Part of the stimulatory effect of acetylcholine is derived from its capacity to counteract the action of Ca at the stabilizing site.