Figure 6-3 Proposed signaling pathways underlying volatile anesthetic (specifically halothane)-induced bronchodilation or inhibition of muscarinic agonist-induced contraction of airway smooth muscle, or both mechanisms. Signal transduction involving Rho protein is supported by work from Warner and coworkers on a role of halothane to decrease Ca²⁺ sensitivity rather than a change in ICa²⁺ content. CaM, calmodulin; ICa²⁺ intracellular Ca²⁺ ; IP3, inositol triphosphate; MLC, myosin light chain; MLCK, myosin light chain kinase; pMLC, phosphorylated myosin light chain; Rho, monomeric G protein; ROK, Rho-associated kinase; RyR, ryanodine channels; SMPP, smooth muscle protein phosphatase; SR, sarcoplasmic reticulum; VDC, voltage-dependent Ca²⁺ channels; encircled plus sign, excitatory action of muscarinic receptor agonist; encircled up arrow, represents activation or increase due to volatile anesthetic; encircled down arrow, inhibition or decrease due to volatile anesthetic. (Adapted from Hanazaki M, Jones KA, Perkins WJ, et al: Halothane increases smooth muscle protein phosphatase in airway smooth muscle. Anesthesiology 94:129, 2001 and from Pabelick CM, Prakash YS, Kannan MS, et al: Effects of halothane on sarcoplasmic reticulum calcium release channels in porcine airway smooth muscle cells. Anesthesiology 95:207, 2001.)