Hypertension, Vol 17, 723-732, Copyright © 1991 by American Heart Association
JT Stull, PJ Gallagher, BP Herring and KE Kamm
For many years the simple view was held that contractile force in smooth
muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+]i). With
the discovery that phosphorylation of myosin light chain by
Ca2+/calmodulin-dependent myosin light chain kinase initiated contraction,
regulation of the contractile elements developed more complex properties.
Molecular and biochemical investigations have identified important domains
of myosin light chain kinase: light chain binding sites, catalytic core,
pseudosubstrate prototope, and calmodulin-binding domain. New protein
phosphatase inhibitors such as okadaic acid and calyculin A should help in
the identification of the physiologically important phosphatase and
potential modes of regulation. The proposal of an attached,
dephosphorylated myosin cross bridge (latch bridge) that can maintain force
has evoked considerable controversy about the detailed functions of the
myosin phosphorylation system. The latch bridge has been defined by a model
based on physiological properties but has not been identified
biochemically. Thin-filament proteins have been proposed as secondary sites
of regulation of contractile elements, but additional studies are needed to
establish physiological roles. Changes in the Ca2+ sensitivity of smooth
muscle contractile elements with different modes of cellular stimulation
may be related to inactivation of myosin light chain kinase or activation
of protein phosphatase activities. Thus, contractile elements in smooth
muscle cells are not dependent solely on [Ca2+]i but use additional
regulatory mechanisms. The immediate challenge is to define their relative
importance and to describe molecular-biochemical properties that provide
insights into proposed physiological functions.
ARTICLES
Vascular smooth muscle contractile elements. Cellular regulation
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
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