LENGTH-DEPENDENT MODULATION OF SMOOTH-MUSCLE ACTIVATION - EFFECTS OF AGONIST, CYTOCHALASIN, AND TEMPERATURE

We tested the hypothesis that mechanical strain modulates agonist sens itivity of smooth muscle by measuring myosin phosphorylation and contr actile force in bovine tracheal smooth muscle activated by various con centrations of the muscarinic receptor agonist carbachol and at variou s muscle lengths. Increasing carbachol concentration by 10,000-fold di d not restore myosin phosphorylation levels at shorter muscle lengths to the level at optimal length (L-0). Maximum levels of myosin phospho rylation induced by carbachol at 0.6, 0.8, and 1.0 L-0 mere similar bu t became lower at <0.6 L-0. Cytochalasin D significantly attenuated ca rbachol-induced contraction by 54%. In addition, cytochalasin D treatm ent induced a parallel downward shift in the length-myosin phosphoryla tion relation. Lowering temperature from 37 to 23 degrees C did not si gnificantly change the length dependencies of carbachol-induced active force and myosin phosphorylation. These results have led us to conclu de that 1) agonist sensitivity and maximum level of activation las mea sured by myosin phosphorylation) are targets of length-dependent modul ation, 2) actin filaments involved in contraction and length-dependent modulation are distinct in sensitivity to cytochalasin D, and 3) leng th-dependent modulation is relatively temperature insensitive.