title: Regulation of vascular smooth muscle contraction: myosin light chain phosphorylation dependent and independent pathways.
abstract: Ca(2+)-dependent myosin light chain (MLC) phosphorylation is an important step in the initiation of smooth muscle contraction. However, MLC phosphorylation alone cannot account for all aspects of contractile regulation, suggesting the involvement of other elements. In this article we present evidence obtained from Triton X-100 detergent skinned and intact tissue which demonstrates that vascular smooth muscle contraction can be initiated by a Ca(2+)-dependent mechanism that does not require prior MLC phosphorylation. We show that Ca2+ can initiate contractions supported by cytidine triphosphate (CTP) and that these contractions are inhibited by calmodulin antagonists, suggesting a Ca(2+)-calmodulin dependence of force distinct from that for MLC phosphorylation. Evidence is presented to demonstrate that carotid medial fibers contain a mitogen-activated protein (MAP) kinase which is activated by Ca2+ and may catalyze caldesmon phosphorylation. Based in part on our results and those of other investigators, we propose that direct Ca(2+)-calmodulin binding to caldesmon or phosphorylation of caldesmon by a Ca(2+)-dependent MAP kinase disinhibits caldesmon. Disinhibition of caldesmon allows an inherent basal level of actin-activated myosin ATPase activity to be expressed. The result is the slow development of force.
authors.affiliation: Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Moreland
authors.forename: R S
authors.initials: RS
authors.lastname: Moreland
mesh_terms: D000818:Animals; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015879:Myosin Subfragments / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation
chemical_list: D015879:Myosin Subfragments