Calcium Sensitization in Smooth Muscle Involving Regulation of Myosin Light Chain Phosphatase Activity

This chapter describes the molecular basis of Ca²⁺ sensitization in smooth muscle. That the regulation of smooth muscle contraction differs from the strict depolarization- and Ca²⁺-dependent excitation-contraction coupling of striated skeletal and cardiac muscle was evident by the 1960s, but consensus concerning the mechanism responsible did not emerge until the late 1980s. Direct evidence of Ca²⁺ sensitization of the contractile apparatus, and identification of the key mechanisms responsible for myosin light chain phosphatase (MLCP) inhibition, was initially obtained by examining agonist-evoked contraction in smooth muscle tissues treated with membrane permeabilizing agents. Variability in the activation of Ca²⁺ sensitization by excitatory agonists and other stimuli in smooth muscle may derive from differences in the regulation of RhoA activity. RhoGEFs are triggered by activated Gα-subunits, which stimulate their guanine nucleotide exchange activity, facilitating the replacement of GDP with GTP on RhoA.