The paradox of smooth muscle physiology

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (contraction) and the release of force (relaxation). The signaling events that activate contraction include Ca²⁺-dependent myosin light chain phosphorylation. The signaling events that mediate relaxation include the removal of a contractile agonist (passive relaxation) and activation of cyclic nucleotide-dependent signaling pathways in the continued presence of a contractile agonist (active relaxation). The major questions that remain in contractile physiology include (1) how is tonic force maintained when intracellular Ca²⁺ levels and myosin light chain phosphorylation have returned to basal levels; and (2) what is the mechanism of cyclic nucleotide-dependent relaxation? This review focuses on these specific controversies surrounding the molecular mechanisms of contraction and relaxation of vascular smooth muscle.