CALDESMON AND A 20-KDA ACTIN-BINDING FRAGMENT OF CALDESMON INHIBIT TENSION DEVELOPMENT IN SKINNED GIZZARD MUSCLE-FIBER BUNDLES

Caldesmon is known to inhibit actin-activated myosin ATPase activity i n solution, to inhibit force production when added to skeletal muscle fibers, and, to alter actin movement in the in vitro cell motility ass ay. It is less clear that caldesmon can inhibit contraction in smooth muscle cells in which caldesmon is abundant. We now show that caldesmo n and its 20-kDa actin-binding fragment are able to inhibit force in c hemically skinned gizzard fiber bundles, which are activated by a cons titutively active myosin light-chain kinase in the presence and absenc e of okadaic acid. This inhibitory effect is reversed by high concentr ations of Ca2+ and calmodulin. Therefore, caldesmon may act by increas ing the level of myosin phosphorylation required to obtain full activa tion. Our results also suggest that caldesmon does not act to maintain force in smooth muscle by cross-linking myosin with actin since compe tition of binding of caldesmon with myosin does not cause a reduction in tension.