Force augmentation and stimulated actin polymerization in arterial smooth muscle contraction

Sustained stimulation of arterial smooth muscle induces contraction and increases in actin polymerization, a process that we term "stimulated actin polymerization." Tyrosine phosphorylation of the scaffolding protein paxillin is thought to be an important regulator of actin polymerization in multiple cell types. Noise temperature and hysteresivity are proposed to be mechanical estimates of changes in cytoskeletal rheology, including that occurring with changes actin polymerization.;Y118 paxillin phosphorylation, actin polymerization, noise temperature, hysteresivity, and phase angle did not significantly change during the initial phase of a stimulus-induced carotid arterial smooth muscle contraction, but were altered after full force development, indicating that they may not be required for the initial phase of contraction. These data suggest that paxillin phosphorylation may regulate actin polymerization and cytoskeletal rheology and that stimulated actin polymerization could be involved in the sustained phase of smooth muscle contraction.;The phenomenon of post-tetanic potentiation has been observed in both skeletal and cardiac muscle. We describe a similar phenomenon in swine carotid arterial smooth muscle, in which submaximal K+ depolarization increases the force generation of a subsequent maximal depolarization by approximately 15% -- we term this "force augmentation." Force augmentation was not associated with a significant increase myosin light chain phosphorylation or shortening velocity, suggesting that the augmented force was not caused by higher crossbridge phosphorylation or crossbridge cycling rates. We found that the characteristics of the tissue prior to the maximal K+ depolarization predicted the degree of force augmentation. These data suggest that stimulated actin polymerization may produce a substrate for increased crossbridge mediated force.;To test whether stimulated actin polymerization is involved in force augmentation, we altered stimulated actin polymerization by adjusting tissue length and then measured the effect on force augmentation. At optimal tissue length and short tissue length, force augmentation was observed and was associated with increased prior stimulated actin polymerization. At long tissue lengths, force augmentation was not observed and there were no prior changes in stimulated actin polymerization. Tissues contracted faster at longer tissue lengths; contractile rate correlated with prior Y118 paxillin phosphorylation. These data suggest that force augmentation is regulated by stimulated actin polymerization.