Tissue length modulates “stimulated actin polymerization,” force augmentation, and the rate of swine carotid arterial contraction

Abstract

Tejani AD, Walsh MP, Rembold CM. Tissue length modulates "stimulated actin polymerization," force augmentation, and the rate of swine carotid arterial contraction. Am J Physiol Cell Physiol 301: C1470 -C1478, 2011. First published August 24, 2011 doi:10.1152/ajpcell.00149.2011.-"Stimulated actin polymerization" has been proposed to be involved in force augmentation, in which prior submaximal activation of vascular smooth muscle increases the force of a subsequent maximal contraction by ϳ15%. In this study, we altered stimulated actin polymerization by adjusting tissue length and then measured the effect on force augmentation. At optimal tissue length (1.0 L o), force augmentation was observed and was associated with increased prior stimulated actin polymerization, as evidenced by increased prior Y118 paxillin phosphorylation without changes in prior S3 cofilin or cross-bridge phosphorylation. Tissue length, per se, regulated Y118 paxillin, but not S3 cofilin, phosphorylation. At short tissue length (0.6 L o), force augmentation was observed and was associated with increased prior stimulated actin polymerization, as evidenced by reduced prior S3 cofilin phosphorylation without changes in Y118 paxillin or cross-bridge phosphorylation. At long tissue length (1.4 L o), force augmentation was not observed, and there were no prior changes in Y118 paxillin, S3 cofilin, or cross-bridge phosphorylation. There were no significant differences in the cross-bridge phosphorylation transients before and after the force augmentation protocol at all three lengths tested. Tissues contracted faster at longer tissue lengths; contractile rate correlated with prior Y118 paxillin phosphorylation. Total stress, per se, predicted Y118 paxillin phosphorylation. These data suggest that force augmentation is regulated by stimulated actin polymerization and that stimulated actin polymerization is regulated by total arterial stress. We suggest that K ϩ depolarization first leads to cross-bridge phosphorylation and contraction, and the contraction-induced increase in mechanical strain increases Y118 paxillin phosphorylation, leading to stimulated actin polymerization, which further increases force, i.e., force augmentation and, possibly, latch.

Cytoskeletal Reorganization Evoked by Rho-associated kinase- and Protein Kinase C-catalyzed Phosphorylation of Cofilin and Heat Shock Protein 27, Respectively, Contributes to Myogenic Constriction of Rat Cerebral Arteries

“…9, A and C). The present finding of increased cofilin phosphorylation in the myogenic response differs from previous reports showing decreased levels of phospho-cofilin in tracheal and conduit arterial smooth muscle treated with constrictor agonists (44,56). For this reason, we performed an additional set of experiments in which RMCAs were exposed to 5-HT (1 M) at 10 mm Hg.…”

“…How- ever, the level of LC 20 phosphorylation declines markedly during sustained contraction, but force production is maintained (57,58,61,62). Several mechanisms have been postulated to account for the lack of correlation between phospho-LC 20 content and force in maintained contraction, including: (i) dephosphorylated "latch bridges" that cycle slowly or not at all (61); (ii) regulation of cross-bridge cycling by thin filament-associated proteins (23); (iii) a slow ADP off rate that is enhanced by the high force-induced strain on smooth muscle cross-bridges (63); and more recently, iv) dynamic reorganization of the actin cytoskeleton to enhance the efficiency of force transmission from the contractile apparatus to the cell membrane and extracellular matrix (24,25,56,62,64). Our findings support the view that intravascular pressure modulates the dynamics of actin polymerization via cellular signaling through ROK and PKC.…”

“…Two cytoskeleton-associated proteins, cofilin and HSP27, were previously identified as potential mediators of ROK-and PKC-dependent control of actin polymerization in smooth muscle contraction (44,55,56), but their role in the myogenic response of resistance arteries has not been assessed. Fig.…”

The AMP-Related Kinase (AMPK) Induces Ca 2+ -Independent Dilation of Resistance Arteries by Interfering With Actin Filament Formation

“…However, one vascular study also reported decreased phosphorylation with contraction. 49 The reason for that is not clear at present but may be because of time-, stimulus-, tissue-, or species-dependent variations.…”

The Role of Actin Filament Dynamics in the Myogenic Response of Cerebral Resistance Arteries

“…27 There are likely several important substrates of these activated tyrosine kinases, but only some have been identified. Candidates, based on agonist-and depolarization-induced tyrosine phosphorylation in airway and vascular smooth muscles, include the cytoskeletal proteins paxillin [28][29][30] and talin, 31 the adapter protein p130 Crkassociated substrate (CAS) 32 and p42/44 mitogen-activated protein kinases (MAPKs). 33 Stimulation of a 5 b 1 integrin has been implicated in activation of the L-type Ca 2 þ channel in vascular myocytes via a tyrosine phosphorylation cascade involving FAK, Src, and various focal adhesion proteins, such as paxillin and vinculin.…”