Actin polymerization stimulated by contractile activation regulates force development in canine tracheal smooth muscle.
1. The role of actin polymerization in the regulation of smooth muscle contractility was investigated in canine trachealis muscle strips. The effect of contractile activation on the content of monomeric globular (G)-actin was estimated by the method of DNase I inhibition. The G-actin content was 30 % lower in extracts of muscle strips activated with 10-4 M acetylcholine (ACh) than in extracts from unstimulated muscle strips. The decrease in G-actin in response to contractile stimulation was prevented by latrunculin-A, an agent that prevents actin polymerization by binding to G-actin monomers. 2. The inhibition of actin polymerization by latrunculin-A markedly depressed force development in response to ACh but had no effect on ACh-induced myosin light chain (MLC) phosphorylation. Latrunculin also suppressed the length sensitivity of force during ACh-induced isometric contractions. The actin-capping agent cytochalasin-D also markedly inhibited force and caused only a slight decrease in MLC phosphorylation. Cytochalasin-D also inhibited force in alpha-toxin-permeabilized muscle strips that were activated either by Ca2+ or by ACh at constant pCa. No disorganization of smooth muscle cell ultrastructure was detected by electron microscopy or by immunofluorescence microscopy of muscles treated with either agent. 3. The results suggest that the polymerization of actin is stimulated by the contractile activation of tracheal smooth muscle and that this actin polymerization contributes directly to force development. In addition, actin filament remodelling contributes to the length sensitivity of tracheal smooth muscle contractility.
Mehta
D
D
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Gunst
S J
SJ
D000109:Acetylcholine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015638:Cytochalasin D / Q000378:metabolism; D004285:Dogs; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014132:Trachea / Q000378:metabolism
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018994:Myosin Light Chains; D011108:Polymers; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; D000109:Acetylcholine; C037067:latrunculin A