Fig. 10. Analysis of the effective inhibitor concentrations of CaMKII and mitogen-activated kinase p38 with respect to anesthetic concentrations and proposed signaling pathways. Effective [Inhibitor] (μm) = effective inhibitor concentration in μm to prevent the relaxation induced by the anesthetics derived from figs. 5, 6, and 8; KN-93 (open circles ) = a CaMKII inhibitor competing at the calmodulin site; CKIINtide (filled circles ) = the peptide of the inhibitor protein of CaMKII binding to the catalytic site of autophosphorylated CaMKII (CaMKII-p); SB20358 (x ) = an inhibitor of p38 MAP kinase; MLCK-p(−) = phosphorylated myosin light chain kinase (MLCK-p), resulting in decreased MLCK activity; MLC-p(−) = decreased phosphorylated myosin light chains. A  and B  show a similar pattern of effective concentrations of KN-93 and SB20358 as a direct function of isoflurane (A ), those of CKIINtide and SB20358 as a direct function of halothane (B ). This similarity in patterns between inhibitors of CaMKII and p38 suggests that Ca²⁺activates CaMKII via  p38 signaling leading to relaxation (C ). In contrast, at higher Ca²⁺(released by halothane), CaMKII undergoes autophosphorylation to a higher CaMKII activity, 10which phosphorylates MLCK, resulting in decreased MLCK activity and decreased myosin light chain phosphorylation, 30leading to relaxation (D ).