COLONIC SMOOTH-MUSCLE - CONTRACTILE PROTEINS, SHORTENING VELOCITY, AND REGULATION

Smooth muscle in megacolon was studied in the lethal spotted mouse and its normal sibling. In megacolon, structural remodeling and a very la rge increase in total protein content are associated with some changes in the contractile protein isoform composition. 1) There is a higher actin concentration in megacolon, primarily caused by a larger proport ion of gamma-isoforms. 2) There was no difference in myosin concentrat ion or in SM1/SM2 heavy chains in megacolon and normal muscle contract ile proteins. 3) Only LC17a essential Light chain is present in both n ormal and megacolon. 4) The 25- to 50-kDa 5'-insert occurs in 15-20% o f the myosin in normal colon, compared with 5- to 10-fold lower amount s in megacolon. In permeabilized muscles there was no significant diff erence in unloaded shortening velocity (V-o) with maximal thiophosphor ylation of the 20-kDa Light chains, nor was there significant differen ce in the force vs. Ca2+ and force vs. myosin light chain phosphorylat ion relationships. At approximate to 60% myosin Light chain phosphoryl ation after Ca2+ activation, V-o of megacolon was approximately two ti mes faster than V-o of normal muscle. These cellular changes largely a ccount for the higher propulsive velocity of the colon in situ. The di stribution of myosin and actin isoforms and the lack of a simple relat ionship between myosin light chain phosphorylation and V-o point to th e operation of additional regulatory processes.