Effects of different expression and posttranslational modifications of myosin light chains on contractility of skinned human cardiac fibers

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Abstract
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-iso forms 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.