Desensitization and muscarinic re-sensitization of force and myosin light chain phosphorylation to cytoplasmic Ca2+ in smooth muscle

In alpha-toxin-permeabilized guinea-pig ileum smooth muscle, a step increase in Ca2+ caused a rapid rise in force and myosin light chain (LC20) phosphorylation, followed by their spontaneous decline to a low steady level even though Ca2+ remained constant. Carbachol resensitized the muscles to Ca2+, causing an increase in both the steady state force and LC20 phosphorylation at constant Ca2+. In beta-escin permeabilized preparations, calmodulin and okadaic acid converted the phasic responses to Ca2+ to more tonic ones. We conclude that Ca2(+)-sensitivity of force is modulated through changes in LC20 kinase/phosphatase activity ratio by Ca2+ itself (desensitization) and by agonists (sensitization).