Cooperative Mechanisms in the Regulation of Smooth Muscle Contraction

Abstract

In 1930, Bozler reported that smooth muscle was unique in that it could maintain force with a very low energy expenditure (Bozler, 1930). More recent studies have extended this pioneering work to show that the economy of force maintenance of mammalian smooth muscle can vary to a large extent during the course of an isometric contraction (for review see Butler and Siegman, 1985). Crossbridge cycling rate varies independently of the ability to maintain maximum force, and the underlying regulatory mechanisms are not fully understood. It is known that phosphorylation of the 20 kDa light chain of myosin is central to the process of regulation, but details remain elusive. In vitro biochemical experiments have shown that phosphorylation increases the actin-activated myosin ATPase activity (for review see Hartshorne, 1987). To our knowledge, there has been no study showing that contraction of smooth muscle can occur without some increase in myosin light chain phosphorylation. However, high force can be generated with very low degrees of myosin light chain phosphorylation (Moreland and Moreland, 1987; Ratz and Murphy, 1987). Although there are some important exceptions, in general, the maximum velocity of shortening and energy usage are high under conditions when the degree of light chain phosphorylation is high. The major question that really distills from all of the above is what role does myosin light chain phosphorylation play in the regulation of force output and crossbridge cycling rate?