Monophosphorylation of myosin light chain isoforms enhances calcium sensitivity and force generation in human cardiac fibers, providing mechanistic insight into cardiac contractility which may be impaired in heart failure.
In the human ventricle two isoforms of the phosphorylatable myosin light chain (MPLC) are expressed. These two forms are designated with increasing acidity as LC-2 and LC-2*. In the normal human heart the relation between LC-2/LC-2*-expression is 70/30, suggesting the existence of three different myosin isoenzymes (MPLC-polymorphism) in the normal human ventricle. Both ventricular MPLC-isoforms are monophosphorylated, the LC-2 being higher phosphorylated than the LC-2*. In some patients with heart failure both MPLC isoforms were found to be completely dephosphorylated. In the human atrium a MPLC isoform is expressed which is different from the ventricular MPLC isoforms. The atrial MPLC isoform is mono- and diphosphorylated. Mono-phosphorylation of both the ventricular MPLC isoforms and the atrial MPLC isoform increased responsiveness as well as sensitivity of isometric tension generation of skinned fibers to Ca2+. Part of this effect could be explained by changing the cross-bridge-cycling rate: MPLC increased fapp, the rate-constant for the transition of cross-bridges from the non-force into the force-generating state, thus increasing the amount of force-generating cross-bridge states at a given Ca2+. Monophosphorylation of the MPLC isoforms did not change maximal shortening velocity.
Ingo Morano (1992) studied this question.