Variability and adaptation in the contractile system of smooth muscle

Abstract: This thesis examines the cellular and molecular mechanisms involved in the large diversity of the contractile properties in smooth muscle. Six studies, I-VI, are included. I: a slow smooth muscle (aorta) has a different nucleotide and phosphate dependence compared to a fast type (taenia coli). A slow ADP-release can be one mechanism responsible for the lower shortening velocity of aorta. II: treatment with thyroid hormone in vivo leads to a change in the myosin isoform composition, higher shortening velocity and altered sensitivity to phosphate in smooth muscle. III: hypertrophying intestinal smooth muscle has lower shortening velocity, higher sensitivity to ADP and altered myosin isoform composition compared to normal tissue. IV: calcium transients were similar for smooth muscle tissues with non-muscle and smooth muscle myosin. In fully activated, permeabilised preparations, the sensitivity to ADP was higher for non-muscle compared to smooth muscle myosin, suggesting that a slower ADP-release might be an explanation for the low velocity of non-muscle myosins. The isometric force of non-muscle myosin was much less inhibited by phosphate. V: expression of the intermediate filament protein desmin increased with decreasing size in the arterial tree, down to microarteries. Desmin has a role in active and passive tension development in the microarteries, but not in the aorta or the mesenteric artery. VI: a novel in vitro knock-out technique to remove beta1-integrin in smooth muscle tissue was introduced. Beta1-integrin depletion leads to decreased active force, suggesting a role for beta1-integrin in force generation, or in the maintenance of a contractile phenotype.