Regulation of Smooth Muscle Contractile Elements by Second Messengers

In smooth muscle cells, development of force results from MgA TP-dependent cyclic interactions of myosin in thick filaments with actin in thin filaments. The force of contraction, in turn, is regulated by the concentration of free Ca2+ surrounding these myofilaments. The purposes of the present chapter are to discuss (a) Ca2+ -dependent mechanisms other than myosin light chain phosphorylation by which contractile force in smooth muscle may be reg­ ulated, and (b) other second messenger mechanisms that regulate contractile elements or the myosin kinase/phosphatase system . Since the discovery that phosphorylation of the 20-kDa light chains of myosin by Ca2+ /calmodulin-dependent myosin light chain kinase allows smooth muscle myosin MgATPase to be activated by actin, many in­ vestigators have studied the relationship between light chain phosphorylation and active force in smooth muscle (reviewed in 42; Hai & Murphy, this volume). It is generally accepted that myosin phosphorylation and de­ phosphorylation are sufficient to regulate contraction. While myosin phos­ phorylatiOn/dephosphorylation may be the dominant regulatory pathway, the coexistence of thin-filament linked regulation is not ruled out (51).