HYPERTROPHY OF COLONIC SMOOTH-MUSCLE - STRUCTURAL REMODELING, CHEMICAL-COMPOSITION, AND FORCE OUTPUT

The cellular basis of adaptations occurring during the development of megacolon was studied with the lethal spotted mouse model. Age-depende nt changes in the length-force characteristics of the colon reach a st eady state by 3-4 mo and include an increased relative force developme nt at very short muscle lengths. In megacolon the following occur: 1) structural remodeling expressed as a greater increase in the fraction of maximum force production at short lengths, a shift of optimum lengt h (L-o) to longer lengths, and no change in force per square centimete r; 2) hypertrophy and hyperplasia of both circular and longitudinal mu scle; 3) high resting compliance consistent with no disproportionate c hange in collagen or elastin composition; 4) marked distension so that in situ circumference approximate to 1.8 L-o, where active force prod uction is low, and 5) slack length approximate to 0.65 L-o, as in norm al colon. Biochemical remodeling in megacolon includes disproportionat e increases in ATP and phosphocreatine concentration, with 3.5-fold mo re preformed phosphagen than in normal colon. The myosin concentration is the same in both muscles, but the actin concentration is 1.5-fold greater in megacolon. Most of the cellular changes in megacolon would facilitate high active force output from the muscle at much larger int estinal diameters.